Liver enzymes after short-term acetaminophen error in critically ill children: a cohort study.

Drug-associated harm is common but difficult to detect in the hospital setting. In critically ill children, we sought to evaluate drug-associated hepatic injury following enteral acetaminophen error, defined as acetaminophen dosing that exceeds daily maximum recommendations. This retrospective cohort study took place in two pediatric intensive care units within a pediatric hospital center. The included patients are children (< 18 years of age) admitted to the pediatric and cardiac intensive care unit between January 2008 and January 2018, and receiving enteral acetaminophen. We defined acetaminophen dosing error as exceeding daily acetaminophen dosing by > 10% the upper limit of maximum recommended dose for weight and age (> 82.5 mg/kg/day or > 4400 mg/day). We included 14,146 admissions, who received 147,485 doses of acetaminophen. Acetaminophen dosing errors occurred 1 in every 9.5 patient-days on acetaminophen. ALT and AST decreased significantly over the course of ICU admission (p < 0.0001). In patients with acetaminophen errors, ALT and AST measured in the 24 to 96 h post error were not significantly different than when measured outside this window. A sensitivity analysis using > 100 mg/kg/day as the upper daily acetaminophen error cut-off did not reveal any subsequent significant increase in ALT or ALT in the 24 to 96-h post-error window, compared to measurements taken outside the window. CONCLUSION: Although the administration of acetaminophen in critically ill children frequently exceeds the daily recommended limit and vigilance is needed, we did not find any associated increase in liver transaminases following acetaminophen errors. WHAT IS KNOWN: • Acetaminophen dosing errors are common in pediatric outpatients. • Excessive acetaminophen dosing can be associated with harm, including hepatic injury. WHAT IS NEW: • Exceeding daily acetaminophen dosing limit occurs 1 in every 9.5 patient-days in children admitted to the critical care unit. • In patients with daily dose excess of acetaminophen, we did not find a significant increase in the measured liver enzymes in the 24 to 96 h following the overdosing.

Resident competencies before and after short intensive care unit rotations: a multicentre pilot observational study.

PURPOSE: Residency programs need to understand the competencies developed by residents during an intensive care unit (ICU) rotation, so that curricula and assessments maximize residents' learning. The primary study objective was to evaluate the feasibility for training programs and acceptability by residents of conducting a multi-competency assessment during a four-week ICU rotation. METHODS: We conducted a prospective, multicentre observational pilot study in three ICUs. During weeks 1 and 4 of an ICU rotation, we conducted repeated standardized assessments of non-critical care specialty residents' competencies in cognitive reasoning (script concordance test [SCT]), procedural skills (objective structured assessment of technical skills [OSATS]-global rating scale], and communication skills through a written test, two procedural simulations, and a simulated encounter with a "family member". The feasibility outcomes included program costs, the proportion of enrolled residents able to complete at least one three-station assessment during their four-week ICU rotation, and acceptability of the assessment for the trainees. RESULTS: We enrolled 63 (69%) of 91 eligible residents, with 58 (92%) completing at least one assessment. The total cost to conduct 90 assessments was CAD 33,800. The majority of participants agreed that the assessment was fair and that it measured important clinical abilities. For the 32 residents who completed two assessments, the mean (standard deviation) cognitive reasoning and procedural skill scores increased between weeks 1 and 4 [SCT difference, 3.1 (6.5), P = 0.01; OSATS difference for bag-mask ventilation and central line insertion, 0.4 (0.5) and 0.6 (0.8), respectively; both P ≤ 0.001]. Nevertheless, the communication scores did not change significantly. CONCLUSIONS: A monthly multi-competency assessment for specialty residents rotating in the ICU is likely feasible for most programs with appropriate resources, and generally acceptable for residents. Specialty residents' cognitive reasoning and procedural skills may improve during a four-week ICU rotation, whereas communication skills may not.

RéSUMé: OBJECTIF: Afin que les programmes de formation et les évaluations maximisent les apprentissages des résidents, les programmes de résidence doivent comprendre quelles compétences sont développées par les résidents pendant un stage à l'unité de soins intensifs (USI). L'objectif principal de cette étude était d'évaluer la faisabilité pour les programmes de formation et l'acceptabilité par les résidents de réaliser une évaluation multi-compétences pendant un stage de quatre semaines à l'USI. MéTHODE: Nous avons réalisé une étude pilote observationnelle prospective multicentrique dans trois USI. Pendant les semaines 1 et 4 du stage à l'USI, nous avons mené des évaluations standardisées répétées des compétences des résidents non inscrits dans une spécialisation en soins intensifs en matière de raisonnement cognitif (test de concordance de script [SCT]), d'habiletés procédurales (évaluation objective structurée des compétences techniques [OSATS] - échelle d'évaluation globale), et d'habiletés de communication via un examen écrit, deux simulations d'intervention, et une rencontre simulée avec un « membre de la famille ¼. Les critères de faisabilité comprenaient les coûts du programme d'évaluation, la proportion de résidents inscrits capables de compléter au moins une évaluation en trois stations au cours de leur stage de quatre semaines à l'USI, et l'acceptabilité de l'évaluation par les résidents. RéSULTATS: Nous avons recruté 63 (69 %) des 91 résidents éligibles, et 58 (92 %) ont complété au moins une évaluation. Le coût total pour réaliser 90 évaluations était de 33 800 CAD. La majorité des participants étaient d'accord que l'évaluation était équitable et qu'elle mesurait d'importantes habiletés cliniques. Chez les 32 résidents ayant complété deux évaluations, les scores moyens (écart type) en matière de raisonnement cognitif et d'habiletés techniques ont augmenté entre les semaines 1 et 4 : différence au SCT, 3,1 (6,5), P = 0,0; différence à l'OSATS pour la ventilation au masque et l'installation d'une voie centrale, 0,4 (0,5) et 0,6 (0,8), respectivement; tous deux P ≤ 0,001. Toutefois, les scores en matière de communication n'ont pas changé de manière significative. CONCLUSION: Une évaluation multi-compétences mensuelle des résidents en spécialisation faisant un stage à l'USI est probablement réalisable dans la plupart des programmes disposant des ressources nécessaires, et elle est généralement acceptable pour les résidents. Le raisonnement cognitif et les habiletés techniques des résidents pourraient s'améliorer pendant un stage de quatre semaines à l'USI, alors que leurs compétences de communication pourraient demeurer inchangées.

A modified Delphi to define drug dosing errors in pediatric critical care.

BACKGROUND: There is no globally accepted definition for dosing error in adult or pediatric practice. The definition of pediatric dosing error varies greatly in the literature. The objective of this study was to develop a framework, informed by a set of principles, for a clinician-based definition of drug dosing errors in critically ill children, and to identify the range that practitioners agree is a dosing error for different drug classes and clinical scenarios. METHODS: We conducted a nationwide three staged modified Delphi from May to December 2019. Expert clinicians included Canadian pediatric intensive care unit (PICU) physicians, pharmacists and nurses, with a least 5 years' experience. Outcomes were underlying principles of drug dosing, and error thresholds, as defined by proportion above and below reference range, for common PICU medications and clinical scenarios. RESULTS: Forty-four participants met eligibility, and response rates were 95, 86 and 84% for all three rounds respectively. Consensus was achieved for 13 of 15 principles, and 23 of 30 error thresholds. An over-dosed drug that is intercepted, an under-dose of a possibly life-saving medication, dosing 50% above or below target range and not adjusting for a drug interaction were agreed principles of dosing error. Altough there remained much uncertainty in defining dosing error, expert clinicians agreed that, for most medication categories and clinical scenarios, dosing over or below 10% of reference range was considered an error threshold. CONCLUSION: Dosing principles and threshold are complex in pediatric critical care, and expert clinicians were uncertain about whether many scenarios were considered in error. For most intermittent medications, dosing over 10% below or above reference range was considered a dosing error, although this was largely influenced by clinical context and drug properties. This consensus driven error threshold will help guide routine clinical dosing practice, standardized reporting and drug quality improvement in pediatric critical care.

The Association of Hospital Rate of Delayed Epinephrine Administration With Survival to Discharge for Pediatric Nonshockable In-Hospital Cardiac Arrest.

OBJECTIVES: To evaluate the variation of hospital rates of delayed epinephrine administration in pediatric patients with nonshockable in-hospital cardiac arrest, and the association of those rates with event, 24-hour, and overall survival to hospital discharge. DESIGN: A retrospective evaluation was performed. Delayed epinephrine was defined as greater than 5 minutes between the time the need for chest compressions was identified and epinephrine was administered. The main outcome was the association of hospital rate of delayed epinephrine administration with survival to hospital discharge. Secondary outcomes were event and 24-hour survival. Evaluation used hierarchical logistic regression and included 13 patient/event-level and seven hospital-level factors. SETTING: Hospitals with greater than 6 months data in the American Heart Association's Get With the Guidelines-Resuscitation registry (2000-2016) and greater than or equal to five total pediatric cardiac arrests with nonshockable rhythm. PATIENTS: Children less than 18 years old with index nonshockable in-hospital cardiac arrest treated with greater than or equal to one epinephrine dose. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-thousand four-hundred sixty-two patients at 69 hospitals were included: 218 patients (14.9%) had epinephrine delay rates ranging from 0% to 80% of events (median, 15.6%; interquartile range, 7-25%). The median and interquartile range of hospital level delay was 16% (7-25%). Patient/event-level predictors of delayed epinephrine were asystole (odds ratio, 1.54 [95% CI, 1.10-2.16]) and insertion of an endotracheal tube (odds ratio, 1.86 [95% CI, 1.27-2.73]). Hospital size less than 200 compared with greater than or equal to 500 beds (odds ratio, 3.07 [95% CI, 1.22-7.73]) and ICU location (odds ratio, 0.51 [95% CI, 0.36-0.74]) were associated with epinephrine delay rates. After adjustment, increasing quartiles of epinephrine delay were associated with lower patient and hospital-level return of spontaneous circulation (p = 0.019, p = 0.006) and 24-hour survival (p = 0.018, p = 0.002) respectively, but not survival to discharge (p = 0.20, p = 0.24). CONCLUSIONS: Delayed epinephrine administration following pediatric nonshockable in-hospital cardiac arrest varies significantly between hospitals. Hospitals with higher rates of delayed epinephrine administration had worse patient- and hospital-level outcomes after adjusting for multiple patient- and hospital-level factors. Delayed epinephrine administration may directly contribute to increased mortality risk and/or may be a marker of unmeasured elements of hospital resuscitation performance.

A systematic review of the effects of resident duty hour restrictions in surgery: impact on resident wellness, training, and patient outcomes.

BACKGROUND: In 2003, the Accreditation Council for Graduate Medical Education (ACGME) mandated 80-hour resident duty limits. In 2011 the ACGME mandated 16-hour duty maximums for PGY1 (post graduate year) residents. The stated goals were to improve patient safety, resident well-being, and education. A systematic review and meta-analysis were performed to evaluate the impact of resident duty hours (RDH) on clinical and educational outcomes in surgery. METHODS: A systematic review (1980-2013) was executed on CINAHL, Cochrane Database, Embase, Medline, and Scopus. Quality of articles was assessed using the GRADE guidelines. Sixteen-hour shifts and night float systems were analyzed separately. Articles that examined mortality data were combined in a random-effects meta-analysis to evaluate the impact of RDH on patient mortality. RESULTS: A total of 135 articles met the inclusion criteria. Among these, 42% (N = 57) were considered moderate-high quality. There was no overall improvement in patient outcomes as a result of RDH; however, some studies suggest increased complication rates in high-acuity patients. There was no improvement in education related to RDH restrictions, and performance on certification examinations has declined in some specialties. Survey studies revealed a perception of worsened education and patient safety. There were improvements in resident wellness after the 80-hour workweek, but there was little improvement or negative effects on wellness after 16-hour duty maximums were implemented. CONCLUSIONS: Recent RDH changes are not consistently associated with improvements in resident well-being, and have negative impacts on patient outcomes and performance on certification examinations. Greater flexibility to accommodate resident training needs is required. Further erosion of training time should be considered with great caution.

Death and Dying in Hospitalized Pediatric Patients: A Prospective Multicenter, Multinational Study.

Background: For hospitalized children admitted outside of a critical care unit, the location, mode of death, "do-not-resuscitate" order (DNR) use, and involvement of palliative care teams have not been described across high-income countries. Objective: To describe location of death, patient and terminal care plan characteristics of pediatric inpatient deaths inside and outside the pediatric intensive care unit (PICU). Design: Secondary analysis of inpatient deaths in the Evaluating Processes of Care and Outcomes of Children in Hospital (EPOCH) randomized controlled trial. Setting/Subjects: Twenty-one centers from Canada, Belgium, the United Kingdom, Ireland, Italy, the Netherlands, and New Zealand. Measurement: Descriptive statistics were used to compare patient and terminal care plan characteristics. A multivariable generalized estimating equation examined if palliative care consult during hospital admission was associated with location of death. Results: A total of 365 of 144,539 patients enrolled in EPOCH died; 219 (60%) died in PICU and 143 (40%) died on another inpatient unit. Compared with other inpatient wards, patients who died in PICU were less likely to be expected to die, have a DNR or palliative care consult. Hospital palliative care consultation was more common in older children and independently associated with a lower adjusted odds (95% confidence interval) of dying in PICU [0.59 (0.52-0.68)]. Conclusion: Most pediatric inpatient deaths occur in PICU where patients were less likely to have a DNR or palliative care consult. Palliative care consultation could be better integrated into end-of-life care for younger children and those dying in PICU.

The interactions of age, genetics, and disease severity on tacrolimus dosing requirements after pediatric kidney and liver transplantation.

PURPOSE: In children, data on the combined impact of age, genotype, and disease severity on tacrolimus (TAC) disposition are scarce. The aim of this study was to evaluate the effect of these covariates on tacrolimus dose requirements in the immediate post-transplant period in pediatric kidney and liver recipients. METHODS: Data were retrospectively collected describing tacrolimus disposition, age, CYP3A5 and ABCB1 genotype, and pediatric risk of mortality (PRISM) scores for up to 14 days post-transplant in children receiving liver and renal transplants. Initial TAC dosing was equal in all patients and adjusted using therapeutic drug monitoring. We determined the relationship between covariates and tacrolimus disposition. RESULTS: Forty-eight kidney and 42 liver transplant recipients (median ages 11.5 and 1.5 years, ranges 1.5-17.7 and 0.05-14.8 years, respectively) received TAC post-transplant. In both transplant groups, younger children (<5 years) needed higher TAC doses than older children [kidney: 0.15 (0.07-0.35) vs. 0.09 (0.02-0.20) mg/kg/12h, p = 0.046, liver: 0.12 (0.04-0.32) vs. 0.09 (0.01-0.18) mg/kg/12h, p = 0.038]. In kidney but not liver transplants, CYP3A5 expressors needed significantly higher TAC doses than nonexpressors [0.15 (0.07-0.20) vs. 0.09 (0.02-0.35) mg/kg/12h, P = 0.001]. In these patients, age and CYP3A5 genotype were independently associated with TAC dosing requirement. In liver, but not kidney transplant patients, homozygous ABCB1 T-T-T haplotype carriers needed higher TAC doses than noncarriers [0.26 (0.15-0.32) vs. 0.11 (0.01-0.25) mg/kg/12h, p = 0.013]. CONCLUSION: CYP3A5 genotype may explain variation in tacrolimus disposition early after transplant in pediatric kidney recipients, independent of age-related variation. In contrast, in pediatric liver recipients, variation in tacrolimus disposition appears related to age and ABCB1 genotype. These findings illustrate the importance of the interplay among age, genotype, and transplant organ on tacrolimus disposition.

Caregiver knowledge and skills to safely care for pediatric tracheostomy ventilation at home.

OBJECTIVE: Caregivers of children using home mechanical ventilation (HMV) via tracheostomy require appropriate knowledge and skills. Existing training curricula are locally developed and content variable. We sought to develop a competency checklist to inform initial training and subsequent assessment of knowledge and skills of family caregivers. METHODS: We used a 2-step process. Candidate items were generated by synthesis of a scoping review, existing checklists, with additional items suggested by an eight member inter-professional group representing pediatric HMV programs across Canada. Following removal of duplicate items, we conducted a three-round Delphi to gain consensus on items for the KidsVent Checklist. RESULTS: The scoping review and checklists from five HMV programs identified 18 domains and 172 items; one additional domain and 83 additional items were identified by our expert group who also classified domains as mandatory or optional. We recruited 95 clinicians representing 12 Canadian paediatric HMV programs to participate in Delphi round 1 (response rate 72%; 84%, and 100% for subsequent rounds). Importance rating of the 255 items reduced them to 246 items. In the final checklist, the 19 domains comprised 14 mandatory (189 mandatory items) and 5 optional domains (57 optional items). CONCLUSIONS: We have developed the KidsVent checklist using rigorous consensus building methods, informed by participants with diverse geographic and inter-professional representation. This checklist represents knowledge and skills required to safely care for children using tracheostomy ventilation at home. Further study is required to explore the impact of this checklist on outcomes of this growing group of technology-dependent children.

Transfusion-associated graft versus host disease.

OBJECTIVES: To review the epidemiology, pathophysiology, therapeutic and preventive strategies of transfusion associated graft versus host disease (TA-GVHD) and relate the findings to the critically ill child. DESIGN: Review article of published medical literature related to TA-GVHD. DATA SOURCES: Medline, bibliography search, published national and institutional guidelines. STUDY SELECTION: Original publications including prospective studies, case reports, case series, laboratory studies, and animal work. DATA EXTRACTION: Data were extracted manually after we reviewed selected articles and assessed their contribution to knowledge of TA-GVHD. DATA SYNTHESIS: New and significant historic information from the selected publications relating to incidence, therapy, prevention, and complications of preventive therapy of TA-GVHD was incorporated. CONCLUSIONS: Pediatric critical care practitioners should be aware of this preventable but fatal complication of cellular blood product transfusion. High-risk categories include congenital and acquired immunodeficiency, younger age, transfusion of blood donated by family members, and transfusion with fresh whole blood. Children at risk for the development of TA-GVHD include neonates, infants, and children with congenital heart disease, not restricted to children with "classic" DiGeorge syndrome. At present, risk identification and targeted prevention are the only methods to manage TA-GVHD. Aside from minimizing cellular blood product exposure, blood product irradiation is the only established and widely available method to prevent TA-GVHD. Transfusion guidelines need to reflect a balance between the incidence of TA-GVHD and the costs of instituting irradiation to selected groups or as routine transfusion policy.

Prospective observational study on the incidence of medication errors during simulated resuscitation in a paediatric emergency department.

OBJECTIVES: To characterise the incidence and nature of medication errors during paediatric resuscitations. DESIGN: A prospective observational study of simulated emergencies. SETTING: Emergency department of a tertiary paediatric hospital. PARTICIPANTS: Teams that included a clinician who commonly leads "real" resuscitations, at least two assisting physicians, and two or three paediatric nurses. INTERVENTIONS: The teams conducted eight mock resuscitations, including ordering medications. Exercises were videotaped and drugs ordered and administered during the resuscitation were recorded. Syringes and drugs prepared during the resuscitation were collected and analysed for concentrations and actual amounts. MAIN OUTCOME MEASURES: Number and type of drug errors. RESULTS: Participants gave 125 orders for medications. In 21 (17%) of the orders the exact dose was not specified. Nine dosing errors occurred during the ordering phase. Of these errors, five were intercepted before the drug reached the patient. Four 10-fold errors were identified. In nine (16%) out of 58 syringes analysed, measured drug concentrations showed a deviation of at least 20% from the ordered dose. A large deviation (at least 50%) from the expected dose was found in four (7%) cases. CONCLUSIONS: Medication errors commonly occur during all stages of paediatric resuscitation. Many errors could be detected only by analysing syringe content, suggesting that such errors may be a major source of morbidity and mortality in resuscitated children.