Evaluation of a Video-Based Education Intervention for Parents of Children Undergoing Fontan Surgery: A Cluster Randomized Controlled Trial.

Background: Fontan surgery is performed at 2-4 years of age and is the third planned surgical intervention for children with a univentricular heart. Major challenges for children and parents after Fontan include (a) psychological distress, (b) prolonged pleural drainage, and (c) the need for postoperative anticoagulation. The aim of this study was to evaluate a pre-Fontan video-based intervention for parents to address these challenges. Methods: This study is a single-centre mixed-methods cluster randomized controlled trial. The intervention consisted of 3 brief whiteboard videos offered online from preadmission clinic to 1 month postoperatively. The parent's State Trait Anxiety Inventory score and the child's Post Hospital Behaviour Questionnaire score were measured 1 week and 1 month postoperatively. Semistructured interviews were conducted to obtain parental feedback on the videos. Results: We enrolled 26 children (13 female patients; 16 intervention group) and 1 parent per child. Mean State Trait Anxiety Inventory scores were similar between groups at both 1 week (52.8 vs 55.5, P = 0.25) and 1 month postoperatively (50.9 vs 53.9, P = 0.25). Post Hospital Behaviour Questionnaire scores were in the maladaptive range but did not differ between groups. Parents agreed or strongly agreed that the videos were helpful but should be provided earlier in the preoperative process. The main value of the videos was recognized as being a method for standardizing information provided to parents. Conclusions: A video-based education intervention did not impact State Trait Anxiety Inventory or Post Hospital Behaviour Questionnaire scores. However, the majority of parents agreed that the videos were helpful.

Contexte: L'opération de Fontan est réalisée à l'âge de 2 à 4 ans et constitue la troisième intervention chirurgicale planifiée chez les enfants qui présentent un ventricule unique. Les enfants et leurs parents font face à des défis importants après une opération de Fontan, dont a) la détresse psychologique, b) le drainage pleural prolongé et c) la nécessité de recourir à une anticoagulothérapie après la chirurgie. Notre étude visait à évaluer une intervention éducative préopératoire sous forme de vidéos présentées aux parents afin de leur permettre de mieux relever ces défis. Méthodologie: Nous avons mené un essai monocentrique à méthodes mixtes et à répartition aléatoire par grappes avec groupe témoin. L'intervention éducative consistait en une série de trois courtes vidéos sur tableau blanc disponibles en ligne à partir de la consultation clinique de préadmission et jusqu'à un mois après la chirurgie. Les scores des parents à l'inventaire d'anxiété situationnelle et de trait d'anxiété (State Trait Anxiety Inventory) et les scores des enfants à l'évaluation du comportement suivant l'hospitalisation (Post Hospital Behaviour Questionnaire) ont été mesurés une semaine et un mois après l'opération. Des entrevues semi-dirigées ont été réalisées afin de recueillir les commentaires des parents au sujet des vidéos. Résultats: Nous avons recruté 26 enfants (dont 13 filles; 16 enfants ont été affectés au groupe d'intervention éducative) et un parent pour chacun des enfants. Les scores moyens obtenus au State Trait Anxiety Inventory étaient comparables entre les deux groupes une semaine (52,8 vs 55,5, p = 0,25) et un mois (50,9 vs 53,9, p = 0,25) après l'opération. Les scores obtenus au Post Hospital Behaviour Questionnaire se situaient dans la fourchette des comportements mésadaptés, mais ne différaient pas entre les groupes. Les parents étaient d'accord ou fortement d'accord pour dire que les vidéos étaient utiles, mais qu'elles auraient dû être offertes plus tôt dans le processus préopératoire. La valeur principale des vidéos était selon eux qu'il s'agissait d'un moyen d'uniformiser l'information transmise aux parents. Conclusions: Une intervention éducative sous forme de vidéos n'a pas eu d'incidence sur les scores obtenus au State Trait Anxiety Inventory ou au Post Hospital Behaviour Questionnaire. Toutefois, la majorité des parents ont trouvé que les vidéos étaient utiles.

Prospective Exploratory Experience With Bivalirudin Anticoagulation in Pediatric Extracorporeal Membrane Oxygenation.

OBJECTIVES: Objective of this study was to determine if bivalirudin resulted in less circuit interventions than unfractionated heparin. A secondary objective was to examine associations between bivalirudin dose and partial thromboplastin time, international normalized ratio, and activated clotting time. DESIGN: Prospective observational. SETTING: Medical-surgical and cardiac PICUs. PATIENTS: Neonatal and pediatric extracorporeal membrane oxygenation patients who received bivalirudin anticoagulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty extracorporeal membrane oxygenation runs in 18 patients used bivalirudin; 90% were venoarterial. Median (interquartile range) age was 4.5 months (1.6-35 mo). Thirteen patients (72%) had an underlying cardiac diagnosis. Of the 20 runs using bivalirudin, 16 (80%) were initially started on unfractionated heparin and transitioned to bivalirudin due to ongoing circuit thrombosis despite therapeutic anti-Xa levels (n = 13), ongoing circuit thrombosis with unfractionated heparin greater than or equal to 40 U/kg/hr (n = 2), or absence of increase in ACT after bolus of 100 U/kg of unfractionated heparin and escalation of unfractionated heparin infusion (n = 1). Initial bivalirudin dose ranged from 0.2 to 0.5 mg/kg/hr; no bolus doses were used. Median (range) bivalirudin dose was 0.9 mg/kg/hr (0.15-1.6 mg/kg/hr). Median (interquartile range) time on extracorporeal membrane oxygenation was 226.5 hours (150.5-393.0 hr) including 84 hours (47-335 hr) on bivalirudin. Nonparametric results are as follows: the rate of circuit intervention was significantly lower in patients on bivalirudin than on unfractionated heparin (median [interquartile range]: 0 [0-1] and 1 [1-2], respectively; Wilcoxon p = 0.0126). Bivalirudin dose was correlated to PTT (rs = 0.4760; p < 0.0001), INR (rs = 0.6833; p < 0.0001), and ACT (rs = 0.6161; p < 0.0001). Four patients had a significant bleeding complication on bivalirudin. Survival to hospital discharge was 56%. CONCLUSIONS: Bivalirudin appears to be a viable option for systemic anticoagulation in pediatric extracorporeal membrane oxygenation patients who have failed unfractionated heparin, but questions remain namely its optimal monitoring strategy. This pilot study supports the need for larger prospective studies of bivalirudin in pediatric extracorporeal membrane oxygenation, particularly focusing on meaningful monitoring variables.

Prospective Side by Side Comparison of Outcomes and Complications With a Simple Versus Intensive Anticoagulation Monitoring Strategy in Pediatric Extracorporeal Life Support Patients.

OBJECTIVES: A continuous infusion of unfractionated heparin is the most common anticoagulant used for pediatric patients on extracorporeal life support. The objective of this study was to compare extracorporeal life support complications and outcomes between two large-volume pediatric extracorporeal life support centers that use different anticoagulation strategies. DESIGN: Prospective, observational cohort study. SETTING: The University of Michigan used simple anticoagulation monitoring, whereas the University of Alberta used an intensive anticoagulation monitoring strategy. PATIENTS: Pediatric patients on extracorporeal life support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was major bleeding per extracorporeal life support run defined as bleeding that was retroperitoneal, pulmonary, or involved the CNS; bleeding greater than 20 mL/kg over 24 hours; or bleeding that required surgical intervention. Secondary outcomes measured were patient thrombosis per run, circuit thrombosis per run, and survival to hospital discharge per patient. Eighty-eight patients (95 runs) less than 18 years old were enrolled at the two centers over 2 years. The two centers enrolled different extracorporeal life support populations; University of Alberta enrolled more postcardiac surgical patients (74% vs 47%; p = 0.005). The indication for extracorporeal life support support also varied by center (p = 0.04). The two centers used similar proportions of VA extracorporeal life support (p = 0.3). Median (interquartile range) unfractionated heparin doses were similar between University of Michigan and University of Alberta, 30 (21-34) U/kg/hr and 26 (22-31) U/kg/hr, p value equals to 0.3, respectively. Median (interquartile range) antifactor Xa was lower in the University of Michigan cohort (0.23 [0.19-0.28] vs 0.41 [0.36-0.46] U/mL; p < 0.001). There was no significant difference in major bleeding (15% University of Michigan vs 21% University of Alberta; p = 0.6) or in patient thromboses (18% University of Michigan vs 13% University of Alberta; p = 0.5). There was no significant difference in survival to hospital discharge (University of Michigan 63% vs University of Alberta 73%; p = 0.1). CONCLUSIONS: Although this prospective cohort study compared different pediatric extracorporeal life support populations, the results did not identify a significant difference in outcomes between simple and intensive anticoagulation monitoring strategies.

Immunizations in Children Requiring Warfarin Therapy.

Children with conditions requiring chronic warfarin therapy have increased. The importance of receiving immunizations in this population is magnified due to potential weakness in their immune response. There is concern about immunizing on therapeutic anticoagulation due to risk of hematomas and the influence of vaccine on warfarin metabolism. This study evaluated the influence of vaccines on warfarin effect as measured by the International Normalized Ratio and the clinically relevant hematomas or bruising postimmunization. There were no clinically relevant negative outcomes postimmunizations. This study demonstrates that immunizations may be safely administered to children receiving therapeutic warfarin therapy.

Antithrombin concentrate in pediatric patients requiring unfractionated heparin anticoagulation: a retrospective cohort study.

OBJECTIVE: To describe antithrombin levels, altered unfractionated heparin effect (anti-factor Xa activity and activated partial thromboplastin time), and adverse effects post administration of a single high dose of antithrombin concentrate. DESIGN: Retrospective review. PATIENTS: Infants and children with antithrombin levels less than 50% and a subtherapeutic unfractionated heparin effect. SETTING: Quaternary care children's hospital with a dedicated anticoagulation program. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A single high dose of antithrombin concentrate was administered. Antithrombin level, anti-factor Xa, and activated partial thromboplastin times were measured post antithrombin concentrate infusion and daily until stable. One hundred twenty-one patients received 246 doses of antithrombin. Patients were described using two cohorts based on the ability to obtain exact heparin doses. Cohort 1 included all patients between January 2004 and May 2008 when complete heparin dosing was unavailable. Cohort 2 included patients from May 2008 to May 2011 when heparin dose was available. Median age and weight were 3.7 months and 4.1 kg. Mean antithrombin concentrate dose was 222 IU/kg. Mean antithrombin level increased from 0.39 to 1.20 U/mL following antithrombin concentrate administration. In cohort 2, unfractionated heparin doses to achieve a target anti-factor Xa activity pre-post antithrombin concentrate were 28 and 19 U/kg/hr, respectively, for children 12 months old or younger and 25 and 19 U/kg/hr, respectively, for children older than 12 months. There were no hemorrhagic, thrombotic, or allergic events within 1 week of antithrombin concentrate administration. CONCLUSIONS: This is the largest study of antithrombin concentrate evaluation in children. Administration of antithrombin concentrate increases anti-factor Xa activity with lower administered unfractionated heparin doses.

Administration of antithrombin concentrate in infants and children on extracorporeal life support improves anticoagulation efficacy.

Unfractionated heparin (UFH) is required in children on extracorporeal life support (ECLS) to maintain circuit patency. When high-dose UFH is inadequate to maintain an anticoagulant effect, the addition of antithrombin concentrate (ATC) is considered. The objective of this study was to review clinical experience giving 1,000 units (U) of ATC to patients on ECLS and UFH anticoagulation. Specifically, antithrombin (AT) levels pre- and post-administration of high-dose ATC, estimation of the efficacy of high-dose ATC administration as measured by the level of anticoagulation, and the incidence of adverse effects were determined. A retrospective chart review of all infants and children on ECLS who received ATC between June 2008 and May 2011 at Stollery Children's Hospital, Edmonton, Canada, was performed. A total of 78 doses of ATC were administered to 36 patients with a median age of 2.9 months (interquartile range, 0.6-12.6) on ECLS. Mean dose of ATC was 241 U/kg (95% confidence interval, 199-283). Mean AT level pre- and post-administration was 0.40 and 0.93 U/ml, respectively. Mean anti-Xa level pre- and post-AT administration was 0.23 and 0.41 U/ml, respectively. There were no associated acute adverse events. The administration of high-dose ATC decreases UFH dose requirements.

Quality of life in children requiring antithrombotic therapy: development of a measure.

Measurement of quality of life (QOL) has been accepted as an important outcome measure in therapeutic clinical trials. Long-term antithrombotic therapy is hypothesized to induce treatment dissatisfaction and influence QOL. Health-related quality of life (HRQOL) can be measured by an inventory developed specific to the patient condition. Pediatric QOL inventory for children on long-term antithrombotic therapy should assess constructs salient for this population. Creation of an HRQOL measurement inventory requires rigor and methodological adherence. Identification and evaluation of QOL constructs is critical to improve care and is accepted as the "gold standard" measurement for patient-centered outcomes in clinical research. The use of a valid and reliable HRQOL inventory specific for the antithrombotic therapy is required for upcoming clinical trials as it will provide a method to measure change in HRQOL specific to the antithrombotic agent. In this way, it will be possible to provide the child/family with information to make safe and effective therapeutic choices, define future antithrombotic therapy research strategies, and inform decision makers to change policies to improve health care.

Hemostasis and platelet dysfunction in asphyxiated neonates.

Hemostasis is the balance between bleeding and clotting and includes coagulation and fibrinolysis with platelet interactions. Despite developmental hemostasis that describes the major differences between neonates and older children and adults, neonates do not have increased bleeding or clotting unless clinical situations disturb the "balance." Perinatal asphyxia alters the balance of hemostasis, resulting in abnormalities that may result in bleeding and thrombosis. The following discussion will describe normal hemostasis, laboratory measures of hemostasis, developmental hemostasis, and the effects of asphyxia on hemostasis.

Evaluation of enoxaparin dosing requirements in infants and children. Better dosing to achieve therapeutic levels.

Increasing the starting dose of enoxaparin results in the early achievement of therapeutic anti-factor Xa levels in children receiving enoxaparin which is critical for effective therapy and the reduction of venipunctures. The aim of this study was: i) to determine the enoxaparin dose required to achieve therapeutic anti-factor Xa levels in infants and children, and ii) to establish whether increasing the starting dose of enoxaparin influenced the time required to reach the therapeutic range and the number of venipunctures required for dose-adjustment, and iii) the radiographic outcome of the thrombosis, where applicable. A retrospective chart review of children who received enoxaparin was carried out at the Stollery Children's Hospital, Edmonton, Alberta, Canada. Patients treated with standard-dose enoxaparin (1.5 mg/kg for children < or =3 months of age, 1.0 mg/kg for children > or =3 months of age), were compared with children who received a higher initial starting dose of enoxaparin (1.7 mg/kg for children > or =3 months of age, 1.2 mg/kg for children > or =3 months of age). Infants <3 months required an enoxaparin dose of 1.83 mg/kg, and those who received an increased initial enoxaparin dose resulted in faster attainment of therapeutic anti-factor Xa levels requiring significantly fewer venipunctures. Similarly, infants > or =3-12 months, 1-5 years, and 6-18 years, require enoxaparin 1.48 mg/kg, 1.23 mg/kg and 1.13 mg/kg, respectively, in order to achieve a therapeutic anti-factor Xa level. In conclusion, increasing the starting dose of enoxaparin may result in more rapid attainment of therapeutic range with fewer venipunctures, dose adjustments, and without an increase in adverse events.

Accuracy of the CoaguChek XS for point-of-care international normalized ratio (INR) measurement in children requiring warfarin.

Point-of-care INR (POC INR) meters can provide a safe and effective method for monitoring oral vitamin K antagonists (VKAs) in children. Stollery Children's Hospital has a large POC INR meter loan program for children requiring oral VKAs. Our protocol requires that POC INR results be compared to the standard laboratory INR for each child on several consecutive tests to ensure accuracy of CoaguChek XS (Roche Diagnostics, Basel Switzerland) meter. It was the objective of the study to determine the accuracy of the CoaguChek XS by comparing whole blood INR results from the CoaguChek XS to plasma INR results from the standard laboratory in children. POC INR meter validations were performed on plasma samples from two time points from 62 children receiving warfarin by drawing a venous blood sample for laboratory prothrombin (PT)-INR measurements and simultaneous INR determinations using the POC-INR meter. Agreement between CoaguChek XS INR and laboratory INR was assessed using Bland-Altman plots. Bland-Altman's 95% limits of agreement were 0.11 (-0.20; 0.42) and 0.13 (-0.22; 0.48) at the two time points, respectively. In conclusion, the CoaguChek XS meter appraisal generates an accurate and precise INR measure in children when compared to laboratory INR test results.