Growing up with Midazolam in the Neonatal and Pediatric Intensive Care

Swart, Eleonora L.; Slort, Pauline R.; Plötz, Frans B.

doi:10.2174/138920012800840347

Cited by 13 publications

(12 citation statements)

References 54 publications

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“…Very little is known about the pharmacodynamics of midazolam in infants and only two articles are available in literature [54, 63]. Swart et al [63] stated that from the clinical studies it is clear that there is a large variability in response to a given concentration of midazolam.…”

Section: Resultsmentioning

confidence: 99%

Clinical Pharmacology of Midazolam in Neonates and Children: Effect of Disease—A Review

Pacifici

2014

International Journal of Pediatrics

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Midazolam is a benzodiazepine with rapid onset of action and short duration of effect. In healthy neonates the half-life (t 1/2) and the clearance (Cl) are 3.3-fold longer and 3.7-fold smaller, respectively, than in adults. The volume of distribution (Vd) is 1.1 L/kg both in neonates and adults. Midazolam is hydroxylated by CYP3A4 and CYP3A5; the activities of these enzymes surge in the liver in the first weeks of life and thus the metabolic rate of midazolam is lower in neonates than in adults. Midazolam acts as a sedative, as an antiepileptic, for those infants who are refractory to standard antiepileptic therapy, and as an anaesthetic. Information of midazolam as an anaesthetic in infants are very little. Midazolam is usually administered intravenously; when minimal sedation is required, intranasal administration of midazolam is employed. Disease affects the pharmacokinetics of midazolam in neonates; multiple organ failure reduces the Cl of midazolam and mechanical ventilation prolongs the t 1/2 of this drug. ECMO therapy increases t 1/2, Cl, and Vd of midazolam several times. The adverse effects of midazolam in neonates are scarce: pain, tenderness, and thrombophlebitis may occur. Respiratory depression and hypotension appear in a limited percentage of infants following intravenous infusion of midazolam. In conclusion, midazolam is a safe and effective drug which is employed as a sedative, as antiepileptic agent, for infants who are refractory to standard antiepileptic therapy, and as an anaesthetic.

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Section: Resultsmentioning

confidence: 99%

Clinical Pharmacology of Midazolam in Neonates and Children: Effect of Disease—A Review

Pacifici

2014

International Journal of Pediatrics

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“…(14, 34, 35) Midazolam pharmacokinetics and pharmacodynamics have been shown to change with age, leading to significant inter-individual variability. (26, 36, 37) To date, direct comparisons of midazolam and lorazepam have not been made in the PICU population, and data are limited on the use of diazepam in the ICU setting. (38) Consistent with other ICU surveys, we found that diazepam is rarely used as a first-line sedative agent in mechanically ventilated children.…”

Section: Discussionmentioning

confidence: 99%

Sedation, Sleep Promotion, and Delirium Screening Practices in the Care of Mechanically Ventilated Children

Kudchadkar

Yaster

Punjabi

2014

Critical Care Medicine

198

183

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Objective To examine pediatric intensivist sedation management, sleep promotion, and delirium screening practices for intubated and mechanically ventilated children. Design An international, online survey of questions regarding sedative and analgesic medication choices and availability, sedation protocols, sleep optimization, and delirium recognition and treatment. Setting Member societies of the World Federation of Pediatric Intensive and Critical Care Societies were asked to send the survey to their mailing lists; responses were collected from July 2012 to January 2013. Interventions Survey Measurements and Main Results The survey was completed by 341 respondents, the majority of whom were from North America (70%). Twenty-seven percent of respondents reported having written sedation protocols. Most respondents worked in pediatric intensive care units (PICUs) with sedation scoring systems (70%), although only 42% of those with access to scoring systems reported routine daily use for goal-directed sedation management. The State Behavioral Scale was the most commonly used scoring system in North America (22%), with the COMFORT score more prevalent in all other countries (39%). The most commonly used sedation regimen for intubated children was a combination of opioid and benzodiazepine (72%). Most intensivists chose fentanyl as their first-line opioid (66%) and midazolam as their first-line benzodiazepine (86%), and prefer to administer these medications as continuous infusions. Propofol and dexmedetomidine were the most commonly restricted medications in PICUs internationally. Use of earplugs, eye masks, noise reduction, and lighting optimization for sleep promotion was uncommon. Delirium screening was not practiced in 71% of respondent’s PICUs, and only 2% reported routine screening at least twice a day. Conclusions The results highlight the heterogeneity in sedation practices among intensivists who care for critically ill children, as well as a paucity of sleep promotion and delirium screening in PICUs worldwide.

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“…All ventilated piglets were sedated using a loading dose of fentanyl (5 µg/kg) and midazolam (0.2 mg/kg) followed by a maintenance infusion of fentanyl (2 µg/kg/h) and midazolam (6 µg/kg/h for <113d animals and 10 µg/kg/h for 113d animals). This protocol is similar to the current sedation protocol used in preterm infants [15]–[17]. Drug and replacement fluids (10% glucose at a rate of 3 mL/kg/h) were delivered via a 3.5FG dual lumen neonatal umbilical vein catheter (Argyle, Sherwood Medical, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

A Pig Model of the Preterm Neonate: Anthropometric and Physiological Characteristics

et al. 2013

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BackgroundLarge animal models are an essential tool in the development of rationally-based new clinical therapies for preterm infants. We provide a description of the newborn pig as a model of the preterm neonate in terms of growth parameters, physiology and the requirement for intensive care over a range of gestational ages.MethodsTwenty-nine litters of piglets (n = 298) were delivered by caesarean section at six timepoints during gestation from 91d to 113d (term = 115d). Two groups, at 91 and 97d gestation, also received maternal glucocorticoid treatment. At four of these timepoints, piglets (n = 79) were ventilated, sedated and monitored using standard neonatal intensive care techniques for up to 8 h in various experimental protocols.ResultsBody weight increased from mean 697 g (SD 193) at 91d gestation to 1331 g (SD 368) at 113d gestation. Piglets delivered at 97d gestation were able to be resuscitated and kept alive for at least 8 h on respiratory support after surfactant administration. Maternal glucocorticoid treatment 48 h and 24 h hours prior to delivery reduced the requirement for ventilator support and improved cardiovascular stability.ConclusionThe pig provides a relevant model for the study of human preterm physiology and for investigation of novel therapies to improve outcomes.

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Growing up with Midazolam in the Neonatal and Pediatric Intensive Care

Cited by 13 publications

References 54 publications

Clinical Pharmacology of Midazolam in Neonates and Children: Effect of Disease—A Review

Clinical Pharmacology of Midazolam in Neonates and Children: Effect of Disease—A Review

Sedation, Sleep Promotion, and Delirium Screening Practices in the Care of Mechanically Ventilated Children

A Pig Model of the Preterm Neonate: Anthropometric and Physiological Characteristics

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