Evaluation of acquired antithrombin deficiency in paediatric patients supported on extracorporeal membrane oxygenation.

AIMS: There remains a paucity of literature regarding best practice for antithrombin (AT) monitoring, dosing and dose-response in paediatric extracorporeal membrane oxygenation (ECMO) patients. METHODS: We conducted a retrospective cohort study at a quaternary care paediatric intensive care unit in all patients <18 years of age supported on ECMO from 1 June 2011 to 30 April 2020. Adverse events and outcomes were characterized for all ECMO runs. AT activity and replacement were characterized and compared between two clinical protocols. AT activities measured post- vs. pre-AT replacement were compared in order to characterize a dose-response relationship. RESULTS: The final cohort included 191 patients with 201 ECMO runs and 2028 AT activity measurements. The median AT activity was 65% (interquartile range [IQR], 51-82) and 879 (43.3%) measurements met the criteria of deficient. The overall median AT dose and increase in AT activity were 50.6 units/kg/dose (IQR, 39.5-67.2) and 23.5% (IQR, 9.8-36.0), respectively. In the protocol that restricted AT activity measurements to clinical scenarios concerning for heparin resistance, there was significantly higher dosing in conjunction with significantly fewer overall administrations. Approximately one third of AT activity remained deficient after repletion. There was no difference in mechanical complications, reasons for discontinuation of ECMO support, time on ECMO or survival between protocols. CONCLUSIONS: There was a high prevalence of AT deficiency in paediatric ECMO patients. An AT replacement protocol based on evaluating heparin resistance is associated with fewer AT administrations, with similar circuit and patient outcomes. Further data are needed to identify optimal dosing strategies.

Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care Anticoagulation and Thrombolysis.

OBJECTIVE: Thrombotic complications are increasingly being recognized as a significant cause of morbidity and mortality in pediatric and congenital heart disease. The objective of this article is to review the medications currently available to prevent and treat such complications. DATA SOURCES: Online searches were conducted using PubMed. STUDY SELECTION: Studies were selected for inclusion based on their scientific merit and applicability to the pediatric cardiac population. DATA EXTRACTION: Pertinent information from each selected study or scientific review was extracted for inclusion. DATA SYNTHESIS: Four classes of medications were identified as potentially beneficial in this patient group: anticoagulants, antiplatelet agents, thrombolytic agents, and novel oral anticoagulants. Data on each class of medication were synthesized into the follow sections: mechanism of action, pharmacokinetics, dosing, monitoring, reversal, considerations for use, and evidence to support. CONCLUSIONS: Anticoagulants, antiplatelet agents, and thrombolytic agents are routinely used successfully in the pediatric patient with heart disease for the prevention and treatment of a wide range of thrombotic complications. Although the novel oral anticoagulants have been approved for a limited number of indications in adults, studies on the safety and efficacy of these agents in children are pending.

Pharmacokinetics of Human Plasma-Derived Antithrombin in Pediatric Patients Supported on Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) support of critically ill pediatric patients is associated with increased risk of thromboembolic events, and unfractionated heparin is used commonly for anticoagulation. Given reports of acquired antithrombin (AT) deficiency in this patient population and associated concern for heparin resistance, AT activity measurement and off-label AT replacement have become common in pediatric ECMO centers despite limited optimal dosing regimens. We conducted a retrospective cohort study of pediatric ECMO patients (0 to <18 years) at a single academic center to characterize the pharmacokinetics (PK) of human plasma-derived AT. We demonstrated that a two-compartment turnover model appropriately described the PK of AT, and the parameter estimates for clearance, central volume, intercompartmental clearance, peripheral volume, and basal AT input under non-ECMO conditions were 0.338 dL/h/70 kg, 38.5 dL/70 kg, 1.16 dL/h/70 kg, 40.0 dL/70 kg, and 30.4 units/h/70 kg, respectively. Also, ECMO could reduce bioavailable AT by 50% resulting in 2-fold increase of clearance and volume of distribution. To prevent AT activity from falling below predetermined thresholds of 50% activity in neonates and 80% activity in older infants and children, we proposed potential replacement regimens for each age group, accompanied by therapeutic drug monitoring.

Inpatient Transition From Intravenous to Inhaled Treprostinil in a Pediatric Patient.

We report a case of a 7-year old male with idiopathic pulmonary arterial hypertension, successfully transitioned from an intravenous infusion to inhaled treprostinil during inpatient admission, after his intentional removal of multiple central venous catheters. He had no clinical, echocardiographic, or serum biomarker evidence of loss of control of pulmonary arterial hypertension during the 4-day transition. The patient was discharged home without complications, and 3 weeks after discharge the patient's pulmonary hypertension remained well controlled per clinical and echocardiographic evidence, including a significantly improved 6-minute walk distance test.

Medication Errors in Overweight and Obese Pediatric Patients: A Narrative Review.

BACKGROUND: The childhood obesity epidemic in the United States has increased utilization of health care and prescribing of medications in overweight and obese children, yet it is unclear whether this has led to more medication errors. The objective of this study was to review all available literature on incidence and types of medication errors in overweight and obese children. METHODS: A search of MEDLINE, Embase, and Scopus databases was conducted for all studies and oral abstracts through December 2020 reporting medication errors in overweight or obese children aged ≤ 18 years. All studies were identified and extracted via a Covidence database. Two reviewers independently reviewed studies and rated the methodologic quality of those included per GRADE (Grading of Recommendations, Assessment, Development and Evaluations) criteria. RESULTS: The search identified 1,016 abstracts from databases. Following review, full text was obtained for 146 articles, of which 141 were excluded. A total of 5 studies met criteria for inclusion and described dosing errors of antimicrobials, anesthetics, and paracetamol in overweight and obese pediatric patients. Two of the 5 studies compared medication errors in obese to nonobese children, and both found that medication errors (both over- and underdosing) were generally more common among obese children. The identified reasons for medication errors included incorrect dosing weight, incorrect dosing strategy, over- and underdosing with weight-based and flat-fixed dosing, and inapposite use of age-based dosing schemas. CONCLUSION: There is a paucity of patient safety evidence available evaluating medication use in overweight and obese children and associated medication errors. Overweight and obese children may be at increased risk of medication errors, although the clinical significance of this is unknown.

Melatonin Administration Patterns for Pediatric Inpatients in a Tertiary Children's Hospital.

OBJECTIVES: Melatonin has been trialed with reported increasing use for sleep dysregulation and prevention of ICU delirium in critically ill adults; however, reports of use in hospitalized pediatric patients are limited. We anecdotally observed an increase in prescribing of melatonin in our tertiary care children's hospital and therefore aimed to retrospectively characterize prescribing practices over time. METHODS: Melatonin dispensing data over a 4-year time frame were extracted. Melatonin doses were categorized as being either ICU or non-ICU administered and dosed during daytime versus nighttime, respectively. Descriptive statistics were used to characterize patients who were administered melatonin, dosing information, and quantitative change in annual melatonin orders between areas. The comparison of daytime versus nighttime melatonin administrations and ratio of administrations between ICU and non-ICU areas for each study year were compared via χ2 test. RESULTS: Administration of melatonin increased 246.2% between years 1 and 3, with a shift from predominance in ICU to non-ICU areas over the study period (P < .0001). The average dosing varied by age, with the most frequent dose being 5 mg (28.3%), predominantly in patients ≥12 years of age. Ninety-eight percent (n = 9434) of doses were scheduled for nighttime administration, suggesting an indication of sleep regulation. There were significantly more daytime administrations of melatonin in non-ICU areas (P < .0001). CONCLUSIONS: Prescribing of melatonin for pediatric inpatients has increased substantially over a 4-year period, despite limited research on dosing, in this single-center. Further research is needed to determine best practices for melatonin prescribing for hospitalized children.

Melatonin Use in Hospitalized Children for Non-Anesthetic Indications: A Systematic Review.

Melatonin, a potent free radical scavenger, plays an important role in homeostasis of cell and organ physiology. The increased demand and synthesis from the pineal gland during times of oxidative stress suggests a potential benefit of melatonin supplementation during hospitalization for acute illness. Yet, the paucity of clinical studies for non-anesthetic-associated indications in pediatric populations hampers the safe, effective, and consistent use of melatonin. The objective of this study was to systematically review published studies of melatonin use for non-sedative and non-analgesic indications in hospitalized pediatric patients. We conducted a search of PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and Scopus databases for articles on the use of melatonin for pediatric patients in a hospital setting. Thirteen eligible studies, all in neonates, were identified. Data elements extracted included study design, number of study subjects, indication for melatonin therapy, and melatonin regimen (formulation, dosage, and duration). Because study methodologies were very heterogeneous, a quantitative synthesis of the published findings was not possible. The identified studies were therefore categorized by the indication of melatonin (adjuvant-antioxidant or anti-inflammatory therapy) in the following specific disease states: (i) acute infections, (ii) respiratory distress syndrome, (iii) neurologic injury, and (iv) jaundice. The current data suggest that melatonin is safe for use in hospitalized neonates. Melatonin may be beneficial for reducing inflammatory markers in neonatal patients with disease states and clinical sequelae that are associated with increased inflammation and oxidative stress. Melatonin, in conjunction with phototherapy, is not superior to use of vitamin D with phototherapy for treatment of neonatal jaundice. However, studies in other pediatric populations are needed given widespread use across clinical inpatient settings.

Design and Implementation of an Analgesia, Sedation, and Paralysis Order Set to Enhance Compliance of pro re nata Medication Orders with Joint Commission Medication Management Standards in a Pediatric ICU.

BACKGROUND: The use of pro re nata (PRN) medication orders increases nursing flexibility and efficiency of bedside patient care. However, misuse and/or ambiguity of PRN medication orders may increase the propensity for medication errors. The Joint Commission has Medication Management (MM) standards to mitigate such risks. This quality improvement study with a pre-post design aimed to increase compliance of PRN sedative and analgesic orders with use of failure mode and effects analysis (FMEA) and human factors risk assessment methodologies in a pediatric ICU (PICU). METHODS: Staff education and a PICU analgesia, sedation, and paralysis order set, with predefined PRN orders, were implemented to enhance PRN medication compliance with Joint Commission MM standards. The primary goal was to achieve and maintain a weekly average compliance of ≥ 90%. Proportions of compliant PRN analgesic and sedative orders before and after interventions were compared. RESULTS: Weekly average PRN orders compliance increased from 62.0% ± 9.2% to 77.7% ± 10.1% after staff education was implemented (p = 0.013). After order set implementation, weekly average compliance further increased to 93.2% ± 3.6% (p < 0.0001) and remained > 90% until the end of the study period. CONCLUSION: Interdisciplinary synthesis using FMEA and human factors risk assessment is effective for identifying system failure modes associated with Joint Commission MM standard noncompliance. Implementation of an order set with forced functionality to include order information compliant with Joint Commission MM standards can enhance and maintain Joint Commission-compliant PRN medication orders.

Clozapine-induced myocarditis in an adolescent male with DiGeorge Syndrome.

DiGeorge Syndrome (22q11.2 deletion syndrome) is a chromosomal disorder associated with both congenital heart malformations and schizophrenia, which is often treatment-resistant and may warrant treatment with clozapine. Clozapine-induced myocarditis (CIM) is a rare complication of clozapine therapy, with a reported incidence ranging from 0.015% to 3%. Fulminant CIM has a nonspecific presentation in both adult and pediatric populations and a mortality rate approaching 50%. Few cases of pediatric CIM have been documented in the literature. This report highlights a case of CIM in an adolescent male with DiGeorge Syndrome whose clinical course was characterized by a subtle, nonspecific presentation and resolution with supportive care.

Identification of Cost-Saving Opportunities for the Use of Antithrombin III in Adult and Pediatric Patients.

Thrombate III is a human plasma-derived antithrombin III (AT-III) often utilized in patients on extracorporeal membrane oxygenation (ECMO) with suspected AT-III-mediated heparin resistance. It is supplied as 500-U and 1000-U vials, costing US$4.66 per unit. Literature is limited in describing the clinical value of AT-III in relation to its high cost. The primary objective was to determine conditions of use and associated cost of potentially unnecessary utilization of AT-III at The Johns Hopkins Hospital. Secondary objectives included evaluating the effect of AT-III on anticoagulation parameters and the overall cost utilized and wasted on AT-III. A retrospective cohort study was performed. The primary end point was the total cost associated with potentially unnecessary utilization of AT-III. There were 326 doses of AT-III administered to 65 patients in 2014. There were 177 (54%) potentially unnecessary doses associated with a cost of US$541 634. Antithrombin III repletion significantly increased median AT-III levels in non-ECMO and ECMO patients compared to baseline (non-ECMO: 62% vs 81%, P < .01; ECMO: 63% vs 81%, P < .01); however, 37.3% of ECMO and 49% of non-ECMO patients had therapeutic anticoagulation monitoring parameters prior to administration. A total cost of US$688 478 was spent on administered AT-III and US$417 194 (38%) was wasted. Utilizing restriction criteria and a new dosing strategy potentially results in estimated annual savings of US$556 000. Utilizing restriction criteria and alternative dosing strategies to mitigate waste and unnecessary use has the potential to result in significant cost savings.