Drug Administration In Children Research Articles

Prescribing Practices in Pediatrics and Drug Utilization Studies Promoting Pediatric Health

Knowledge of drug administration in children and infants lags behind that of adults for many reasons. These include developmental differences that affect the pharmacodynamic and pharmacokinetic profiles of drugs, ethical and financial reasons, research capabilities, and regulatory guidelines and constraints. Most of the drugs prescribed for children have not been tested in the pediatric population due to the difficulties in carrying out clinical studies in children and ethical issues due to children not being able to make their own decisions to participate in a clinical trial. Epidemiological evaluation of medicine use in elderly is now a highly visible topic, but drug prescribing studies in pediatric patients have been limited. The higher incidence of infections in pediatric population as compared to adults leads to higher prescription of Antimicrobial Drugs (AMDs), at times more than two in single prescription. The use of antibiotics in children has been a major area of concern. . Periodic prescriptions analysis and effective feedback to clinician should be done based on results to ensure rational prescribing and effective health care management, which will ultimately lead to a better child health. In this review article, we will to analyze prescribing practices in pediatrics and drug utilization studies promoting pediatric health.

Quantitative Investigation on Exposure to Potentially Harmful Excipients by Injection Drug Administration in Children Under 2 Years of Age and Analysis of Association with Adverse Events: A Single-Center, Retrospective Observational Study.

Potentially harmful excipients (PHEs) for children have been reported and the need for information collection has been advocated. However, studies on the actual occurrence of adverse events are limited. This study investigated the quantitative exposure of PHEs via injection and their association with adverse events in children under 2years of age. As a single-center observational study, children aged 0-23months received injectable drugs from April 1, 2018, to March 31, 2023 were included. Information on PHE exposure and adverse events after administration were extracted from medical records. Sodium benzoate, benzyl alcohol, ethanol, glycerol, lactose, polyethylene glycol paraben, polysorbate, propylene glycol, sorbitol, sucrose, sulfite, and thimerosal were selected as PHEs. 6265 cases, 333,694 prescriptions, and 368 drugs (264 ingredients) were analyzed. The median age was 0.63years (interquartile range [IQR] 0.1-1.1). 72,133 prescriptions, 132 drugs and 99 ingredients contained PHE; 2,961 cases exposed to PHE and 1825 cases exceeding permitted daily exposure. The drug with the highest number of exposure cases was hydroxyzine, and the highest number of prescriptions was heparin (both drugs contain benzyl alcohol). In association between adverse events and PHE exposure, higher doses in cases of adverse event occurrence were found in benzyl alcohol, glycerol, polyethylene glycol, and polysorbate exposed cases. Among thimerosal-exposed cases, "developmental delay" was more frequent in exposed cases, but the causal relationship was unknown. Further investigation is needed to clarify the relationship between adverse events and PHE exposure. Additionally, more precise information on PDE for pediatrics including neonates is necessary.

Mobile app for the accuracy of emergency drug administration in children's cardiovascular resuscitation : A literature review

<p><strong><em>Background : </em></strong><em>Errors in the calculation of drug titration are one of the causes of medical errors that have an impact on the implementation of cardiopulmonary resuscitation in children. Calculations based on age, child weight and incorrect anthropometric data are what cause medical errors in the administration of emergency drugs in cases of pulmonary cardio resuscitation.</em><em> </em><em>One strategy in utilizing technological advances to minimize the occurrence of medical errors in drug administration with the titration method is to use a dose calculation application for drug titration.</em></p><p><strong><em>Objectives : </em></strong><em>The purpose</em><strong><em> </em></strong><em>of this literature review is to analyze the effect of using drug administration calculation applications for the prevention of medical errors in emergency cases and pediatric cardiopulmonary resuscitation</em><em>. </em></p><p><strong><em>Methods : </em></strong><em>This research method is a literature review using PRISMA analysis with a database of PUBMED, Science Direct, Proquest, Springer, Wiley, Taylor ,and France from 2017-2022</em><em>. </em></p><p><strong><em>Results :</em></strong><em>The use of mobile apps for drug administration or titration in cases of cardiovascular emergency children has proven to be effective and efficient because it can speed up the preparation time with dose accuracy to minimize ischemia assembled hypotension to vital organs and improve the hemodynamic status and maintain neurological status</em><em>. </em></p><strong><em>Conclusions: </em></strong><em>Mobile applications is effective and efficient in preventing medical errors in drug administration with the titration method in cases of pediatric cardiopulmonary resuscitation.</em>

Antibiotics use in children: Practice predictors among mothers of under–fives

In the developing countries, drug administration in children under the age of five is a task mostly undertaken by mothers. Parental practices in the use of antibiotics in children can determine the extent of the therapeutic benefit and the development of resistance. This study investigated mothers’ practices on use of antibiotics in children and determined the possible socio-demographic predictors of good practice.
 Mothers of at least a child under the age of five were interviewed to determine their use of antibiotics in children and summary and inferential statistical analysis were conducted.
 Of the 313 mothers interviewed, 119(38%) had overall poor practice. One hundred and eighty-eight (60.1%) used antibiotics when their children had catarrh and sore throats, 195(62.3%) stopped giving antibiotics when their children felt better before completing the dose, 260(83.1%) saved some antibiotics at home in case of future use, 126(40.3%) gave antibiotics without the doctor’s prescription. Older mothers had a greater likelihood to save some antibiotics at home in case of future use, OR=1.087,95%CI-1.016-1.163, increasing age of first child decreases the odds of requesting antibiotics from the doctor OR=0.989, 95% CI:0.981-0.997 while increasing number of children had almost a two-fold increase on the likelihood to request for antibiotics, OR=1.624,95% CI=1.05-2.386. Attaining a tertiary level of education had over a two-fold (OR=2.337, 95% CI=1.063-5.137) and a three-fold (OR=3.262,95% CI= 1.566-6.802) increase on the odds of giving antibiotics to a child without a doctor’s advice and reading information leaflets respectively. There was a significant difference between self- perceived practice level and actual practice level (P=0.01).
 A good proportion of mothers had less than adequate antibiotics practice levels and some demographic factors predicted practice. Advocacy should be employed to improve practices associated with antibiotics use in children in the developing countries.

In vivo/ex vivo efficacy of artemether\u2013lumefantrine and artesunate\u2013amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso

BackgroundArtemisinin-based combination therapy (ACT) is recommended to improve malaria treatment efficacy and limit drug-resistant parasites selection in malaria endemic areas. 5 years after they were adopted, the efficacy and safety of artemether–lumefantrine (AL) and artesunate–amodiaquine (ASAQ), the first-line treatments for uncomplicated malaria were assessed in Burkina Faso.MethodsIn total, 440 children with uncomplicated Plasmodium falciparum malaria were randomized to receive either AL or ASAQ for 3 days and were followed up weekly for 42 days. Blood samples were collected to investigate the ex vivo susceptibility of P. falciparum isolates to lumefantrine, dihydroartemisinin (the active metabolite of artemisinin derivatives) and monodesethylamodiaquine (the active metabolite of amodiaquine). The modified isotopic micro test technique was used to determine the 50% inhibitory concentration (IC50) values. Primary endpoints were the risks of treatment failure at days 42.ResultsOut of the 440 patients enrolled, 420 (95.5%) completed the 42 days follow up. The results showed a significantly higher PCR unadjusted cure rate in ASAQ arm (71.0%) than that in the AL arm (49.8%) on day 42, and this trend was similar after correction by PCR, with ASAQ performing better (98.1%) than AL (91.1%). Overall adverse events incidence was low and not significantly different between the two treatment arms. Ex vivo results showed that 6.4% P. falciparum isolates were resistant to monodesthylamodiaquine. The coupled in vivo/ex vivo analysis showed increased IC50 values for lumefantrine and monodesethylamodiaquine at day of recurrent parasitaemia compared to baseline values while for artesunate, IC50 values remained stable at baseline and after treatment failure (p > 0.05).ConclusionThese findings provide substantial evidence that AL and ASAQ are highly efficacious for the treatment of uncomplicated malaria in children in Burkina Faso. However, the result of P. falciparum susceptibility to the partner drugs advocates the need to regularly replicate such surveillance studies. This would be particularly indicated when amodiaquine is associated in seasonal malaria chemoprophylaxis (SMC) mass drug administration in children under 5 years in Burkina Faso.Trial registration clinicaltrials, NCT00808951. Registered 05 December 2008,https://clinicaltrials.gov/ct2/show/NCT00808951?cond=NCT00808951&rank=1

Overcome the challenges of drug administration in children by developing age-appropriate formulations

Interest in developing age-appropriate formulations of drugs to optimize pharmacological therapy in children continues to grow. With oral formulations being the most common route of administration, several factors relating to the formulation and bitter taste of drugs can impact the acceptability of medications in children. Approaches to improve medication acceptability include the use of alternative delivery systems, taste-masking strategies and the development of new technologies for formulation preparation.

Current evidence for the use of sugammadex in children.

Summary Sugammadex is a novel pharmacologic agent, which reverses neuromuscular blockade with a mechanism that differs from the commonly used, acetylcholinesterase inhibitors. Although sugammadex has not received approval from the United States Food & Drug administration in children, its use has already been reported to reverse neuromuscular blockade in several clinical scenarios in the pediatric population including the ‘cannot intubate–cannot ventilate’ scenario. To date, there remains limited data from prospective trials in the pediatric-aged patient. Anecdotal use has been reported for the reversal of neuromuscular blockade in difficult clinical scenarios such as children with neuromuscular diseases including myasthenia gravis, Duchenne muscular dystrophy, and myotonic dystrophy.

Concurrent intravenous drug administration to critically ill children: Evaluation of frequency and compatibility

PurposeTo evaluate the frequency of concurrent drug administration and drug-drug incompatibility of concurrently administered drugs in critically ill children based on available references. Materials and methodsWe retrospectively evaluated concurrent intravenous drug administration in children admitted to a single centre. Eligible patients included those admitted to the critical care unit for at least 6-hours in the ten-year period ending 30 July 2015 and received two or more IV drug administrations. Compatibilities were classified using local reference documents. ResultsThe 16,863 eligible patients were admitted to ICU for 2,212,326h and received 3,664,667 concurrent administrations. Concurrent infusions ran for 6,263,600h. There were 2,284,066 (62%) concurrent administrations; 334,144 (9%) were compatible, 293,856 (8%) were incompatible, 293,856 (8%) required pharmacist consultation, and 752,601 (21%) had ‘unknown’ compatibility. Individual patients received a median (IQR) of 33 (10−132) concurrent administrations, comprised of 7 (1−30) concurrent injections 1 (0–5) concurrent infusions and 13 (0–74) concurrently administered injections and infusions. ConclusionsConcurrent IV-drug administration is frequent in critically ill children. Known incompatible concurrent administration occurs, however the compatibilities of many drug-drug pairs were unknown - adding complexity to routine bedside management and identifying information gaps for future research.

Current evidence for the use of sugammadex in children.

Sugammadex is a novel pharmacologic agent, which reverses neuromuscular blockade with a mechanism that differs from the commonly used, acetylcholinesterase inhibitors. Although sugammadex has not received approval from the United States Food & Drug administration in children, its use has already been reported to reverse neuromuscular blockade in several clinical scenarios in the pediatric population including the 'cannot intubate-cannot ventilate' scenario. To date, there remains limited data from prospective trials in the pediatric-aged patient. Anecdotal use has been reported for the reversal of neuromuscular blockade in difficult clinical scenarios such as children with neuromuscular diseases including myasthenia gravis, Duchenne muscular dystrophy, and myotonic dystrophy.

A simple and selective liquid chromatography- tandem mass spectrometry method for determination of ε-aminocaproic acid in human plasma

Understanding the clinical pharmacology of the antifibrinolytic drug epsilon-aminocaproic acid (EACA) is critical for rational drug administration in children. The aim of this study is to develop a reliable assay for the determination of EACA in human plasma. We describe a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay for EACA in human plasma. Sample preparation involved plasma dilution (1:2040), followed by reversed-phase chro- matographic separation and selective detection using tandem mass spectrometry. EACA had a linear range of 1 - 250 µg/mL. The intraday precision based on the standard deviation of replicates of quality control samples ranged from 4.7 to 10.4% and the accuracy ranged from 92-106%. The interday precision ranged from 4.6 to 9.8% and the accuracy ranged from 95-103%. Stability stud- ies showed that EACA was stable during the conditions for sample preparation and storage. The described method is robust and successfully employed for clinical studies of EACA in children.

Anesthesiologists' ability in calculating weight-based concentrations for pediatric drug infusions: an observational study

Study ObjectivesTo assess the ability of anesthesiologists to calculate weight-specific drug concentrations for continuous drug administration in children, and to evaluate the acceptance of an inhouse-developed, computer-based application for calculating drug infusions for pediatric cardiac surgery. DesignObservational study. SettingAnesthesiology department of a tertiary-care medical center in Israel. Participants45 anesthesiology department staff members (attendings and residents). MeasurementsAnesthesiologists were asked to calculate the weight-based amount of drug and the corresponding amount in mL to be drawn from a standard vial and added to a 50-mL syringe in order to reach an infusion rate, where 1 mL/hr corresponds to 1 μg x kg-1 x min-1. The time it took to reach the result was measured. Staff members were also asked to rate the user-friendliness and usability of the program. Main Results41 of the original 42 participants returned the completed questionnaire. Only 6 (15%) of 41 anesthesiologists provided all the correct answers. The mean calculation time required was 205 (±53) seconds. There was no difference in success rate between attendings and residents. Incorrect calculations ranged from a drug concentration 50 times too low up to 56 times too high. Most staff members believed that the computer-based application to perform these calculations reduced errors (65%) and workload (81%), and improved patient treatment (71%). This application was rated as very user-friendly. ConclusionsAnesthesiologists have difficulty calculating pediatric drug concentrations for continuous drug infusions. The correct calculations are time-consuming. Incorrect calculations may lead to dangerously high or low doses. A computer-based application to calculate drug concentrations was rated as very useful and user-friendly.

Complication d’une injection intramusculaire ou syndrome de Nicolau

Nicolau syndrome is a rare, potentially severe complication that may occur after any drug injection, particularly after intramuscular injection. It is characterized by the acute onset of cutaneous and soft-tissue aseptic necrosis. Here, we report the case of a 14-year-old boy diagnosed with Nicolau syndrome on the right lower limb, after a benzathine-penicillin intramuscular injection for suspected rheumatic fever. The short-term progression was marked by uncomplicated rhabdomyolysis and the constitution of homolateral testicular torsion. The cutaneous-muscular disorders evolved favorably under symptomatic treatment. We discuss this insufficiently known complication of intramuscular injection, which may motivate reduced use of this route of drug administration in children and strict adherence to the procedure. Furthermore, it is important to note that Nicolau syndrome may evolve to homolateral testicular torsion, as, to the best of our knowledge, is reported for the first time in this case.

Use of analgesic and anti-inflammatory drugs before assistance in a children’s first aid unit

BACKGROUND AND OBJECTIVES:Drug administration to children is a widely spread practice, however it may lead to several health problems, because in addition to medical guidance it requires attention of parents and caregivers. This study aimed at identifying the prevalence of drug administration in children by their tutors, before medical assistance.METHODS:This is a quantitative descriptive research involving adults who were escorting children, before medical assistance in a Children's First Aid Unit of a medium-sized city of the Vale do Paraiba Paulista in the months of June, July and August 2011, being data recorded by means of a specific form.RESULTS:Participated in the study 105 adults responsible for the children who reported that 71.42% of children were medicated before medical assistance and only 28.58% have not adopted such practice. Most frequent symptom was fever, present in 40% of participants, and drugs used were paracetamol and dipirone.CONCLUSION:Our results allow concluding that there has been a high rate of drug administration to children before medical assistance, with predominance of non-steroid anti-inflammatory drugs, which may be noxious to health. It is clear the need for the adoption of measures which favor the access to health services, in addition to the awareness about the risk of administering drugs without medical prescription.

Population Pharmacokinetics of Epsilon-Aminocaproic Acid in Infants Undergoing Craniofacial Reconstruction Surgery

Background Understanding the clinical pharmacology of the antifibrinolytic epsilon-aminocaproic acid (EACA) is necessary for rational drug administration in children. The aim of this study is to determine the pharmacokinetics (PKs) of EACA in infants aged 6–24 months undergoing craniofacial reconstruction surgery. Methods Cohorts of six infants were enrolled sequentially to one of the three escalating loading dose–continuous i.v. infusion (CIVI) regimens: 25 mg kg−1, 10 mg kg−1 h−1; 50 mg kg−1, 20 mg kg−1 h−1; 100 mg kg−1, 40 mg kg−1 h−1. Plasma EACA concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry assay. A population non-linear mixed effects modelling approach was used to characterize EACA PKs. Results Population PK parameters of EACA were estimated using a two-compartment disposition model with weight expressed as an allometric covariate and an age effect. The typical patient in this study had an age of 38.71 weeks and a weight of 8.82 kg. PK parameters for this typical patient were: pre-/postoperative plasma drug clearance of 32 ml min−1 (3.6 ml kg−1 min−1), inter-compartmental clearance of 42.4 ml min−1 (4.8 ml min−1 kg−1), central volume of distribution of 1.27 litre (0.14 litre kg−1), and peripheral volume of distribution of 2.53 litre (0.29 litre kg−1). Intra-operative clearance and central volume of distribution were 89% and 80% of the pre-/postoperative value, respectively. Conclusions EACA clearance increased with weight and age. The dependence of clearance on body weight supports weight-based dosing. Based on this study, a loading dose of 100 mg kg−1 followed by a CIVI of 40 mg kg−1 h−1 is appropriate to maintain target plasma EACA concentrations in children aged 6–24 months undergoing these procedures.

Development of a brazilian nanoencapsulated drug for schistosomiasis treatment

Schistosomiasis is a parasitic disease that, according to the World Health Organization, constitutes a major public health problem associated with severe morbidity, mostly children in preschool age. The administration of drugs in children always constitutes a difficult task, especially when formulations are not developed specifically for pediatric use, when high doses of drug are required and the drug has a bitter taste, as in the case of praziquantel. Polymer nanoparticles are promising systems for development of encapsulated drugs with low water solubility and bitter taste, due to the good physical and chemical stability, adequate biocompatibility and simple manufacturing processes. Moreover, they can enhance the bioavailability and reduce variability of treatment among patients. Poly(methyl methacrylate) doped with praziquantel was produced through a miniemulsion polymerization process to compose a pediatric pharmaceutical suspension. Nanoparticles were characterized in terms of physico-chemical properties, toxicological properties and biological activity in mice, being concluded that obtained results were satisfactory. The results were encapsulation rate around 90%, absence of chemical interaction drug - polymer and the presence of biological activity. A collaborative approach was used for this development, involving national partnerships and independent funding mechanisms, a powerful pathway for development of drugs for neglected diseases.

Desenvolvimento de um medicamento brasileiro nanoencapsulado para o tratamento da esquistossomose

Schistosomiasis is a parasitic disease that, according to the World Health Organization, constitutes a major public health problem associated with severe morbidity, mostly children in preschool age. The administration of drugs in children always constitutes a difficult task, especially when formulations are not developed specifically for pediatric use, when high doses of drug are required and the drug has a bitter taste, as in the case of praziquantel. Polymer nanoparticles are promising systems for development of encapsulated drugs with low water solubility and bitter taste, due to the good physical and chemical stability, adequate biocompatibility and simple manufacturing processes. Moreover, they can enhance the bioavailability and reduce variability of treatment among patients. Poly(methyl methacrylate) doped with praziquantel was produced through a miniemulsion polymerization process to compose a pediatric pharmaceutical suspension. Nanoparticles were characterized in terms of physico-chemical properties, toxicological properties and biological activity in mice, being concluded that obtained results were satisfactory. The results were encapsulation rate around 90%, absence of chemical interaction drug - polymer and the presence of biological activity. A collaborative approach was used for this development, involving national partnerships and independent funding mechanisms, a powerful pathway for development of drugs for neglected diseases.

FEVER IN CHILDREN WITH RESPIRATORY VIRAL INFECTIONS: EFFECTIVE AND SAFE METHODS OF TREATMENT

One of the most important — the problem of treatment of fever in children with respiratory viral infections — is discussed in this article. It is fever as one of the first symptoms of disease which often frightens parents and leads to inappropriate and excess usage of antipyretic agents, which in its turn can cause unfavorable consequences. The authors represent their own data on frequency of antipyretic drugs usage in children with respiratory viral infections, as well as the answers of pediatricians to the questionnaires on methods of choice in temperature normalization. According to the modern Russian as well as European and American clinical guidelines on treatment of fever in children the management of selection of patients demanding antipyretic treatment is detailed, indications and contraindications to such therapy are described, the most effective methods of temperature normalization in children with acute respiratory infection are discussed. The authors suggested the data on recommended dosages of paracetamol, which were revised in 2011 by the UK Medicines Control Agency, to be very useful. The current information on advantages of ibuprofen in comparison to paracetamol in treatment of fever in children with respiratory viral infections is shown. The main target of this article is understanding and acceptance by pediatricians of the modern recommendation on differential and reasonable approach to administration of antipyretic drugs in children with respiratory viral infections.

Adherence of paediatric nurses to double checking process steps during medication administration in a children's hospital: an observational study

BackgroundMedication errors have been reported to occur in 19.1% drug administration in children.1 Double checking has been recommended to reduce medication errors in children.2 There is insufficient evidence to either...

Population pharmacokinetics of epsilon-aminocaproic acid in infants undergoing craniofacial reconstruction surgery

Understanding the clinical pharmacology of the antifibrinolytic epsilon-aminocaproic acid (EACA) is necessary for rational drug administration in children. The aim of this study is to determine the pharmacokinetics (PKs) of EACA in infants aged 6-24 months undergoing craniofacial reconstruction surgery. Cohorts of six infants were enrolled sequentially to one of the three escalating loading dose-continuous i.v. infusion (CIVI) regimens: 25 mg kg(-1), 10 mg kg(-1) h(-1); 50 mg kg(-1), 20 mg kg(-1) h(-1); 100 mg kg(-1), 40 mg kg(-1) h(-1). Plasma EACA concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry assay. A population non-linear mixed effects modelling approach was used to characterize EACA PKs. Population PK parameters of EACA were estimated using a two-compartment disposition model with weight expressed as an allometric covariate and an age effect. The typical patient in this study had an age of 38.71 weeks and a weight of 8.82 kg. PK parameters for this typical patient were: pre-/postoperative plasma drug clearance of 32 ml min(-1) (3.6 ml kg(-1) min(-1)), inter-compartmental clearance of 42.4 ml min(-1) (4.8 ml min(-1) kg(-1)), central volume of distribution of 1.27 litre (0.14 litre kg(-1)), and peripheral volume of distribution of 2.53 litre (0.29 litre kg(-1)). Intra-operative clearance and central volume of distribution were 89% and 80% of the pre-/postoperative value, respectively. EACA clearance increased with weight and age. The dependence of clearance on body weight supports weight-based dosing. Based on this study, a loading dose of 100 mg kg(-1) followed by a CIVI of 40 mg kg(-1) h(-1) is appropriate to maintain target plasma EACA concentrations in children aged 6-24 months undergoing these procedures.

Transdermal Fentanyl in Deliberate Overdose in Pediatrics

The use of the fentanyl skin patch to provide pain relief in chronic pain conditions and oncology in adult practice has been common for several years, and an increase in use is now being seen in pediatric practice. Its use in drug misuse and suicide has also increased in recent years. We present the case of an adolescent who deliberately overdosed using fentanyl skin patches and describe the implications for management. This report serves to remind clinicians to consider this method of drug administration in children who display signs of opioid toxicity, where overdose may be subsequent to its use in therapy, recreation, or deliberate self-harm.