Inter-individual variation in midazolam clearance in children

Altamimi, Mohammed; Sammons, Helen; Choonara, Imti

doi:10.1136/archdischild-2013-305720

Cited by 23 publications

(16 citation statements)

References 47 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vertical error bars represent the total range of reported clearances or, in the case of one study, the 95% confidence interval. Literature data were obtained after a search of PubMed, with keywords including midazolam, clearance, paediatric, children and pharmacokinetics, and additional studies were identified from reviews and summarizing studies . Studies published up to 25 years ago were included if paediatric subjects in the study received intravenously administered midazolam.…”

Section: Discussionmentioning

confidence: 99%

Predicting CYP3A‐mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure

Brussee

Vet

Krekels

et al. 2017

Brit J Clinical Pharma

View full text Add to dashboard Cite

AimsInflammation and organ failure have been reported to have an impact on cytochrome P450 (CYP) 3A‐mediated clearance of midazolam in critically ill children. Our aim was to evaluate a previously developed population pharmacokinetic model both in critically ill children and other populations, in order to allow the model to be used to guide dosing in clinical practice.MethodsThe model was evaluated externally in 136 individuals, including (pre)term neonates, infants, children and adults (body weight 0.77–90 kg, C‐reactive protein level 0.1–341 mg l–1 and 0–4 failing organs) using graphical and numerical diagnostics.ResultsThe pharmacokinetic model predicted midazolam clearance and plasma concentrations without bias in postoperative or critically ill paediatric patients and term neonates [median prediction error (MPE) <30%]. Using the model for extrapolation resulted in well‐predicted clearance values in critically ill and healthy adults (MPE <30%), while clearance in preterm neonates was over predicted (MPE >180%).ConclusionThe recently published pharmacokinetic model for midazolam, quantifying the influence of maturation, inflammation and organ failure in children, yields unbiased clearance predictions and can therefore be used for dosing instructions in term neonates, children and adults with varying levels of critical illness, including healthy adults, but not for extrapolation to preterm neonates.

show abstract

Section: Discussionmentioning

confidence: 99%

Predicting CYP3A‐mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure

Brussee

Vet

Krekels

et al. 2017

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…Furthermore, the sedation strategy for a patient with severe sepsis should take into account that critical illness reduces midazolam clearance independently of serum creatinine levels and could increase sedation depth. Critical illness thus leads to a great variability in midazolam clearance, as was confirmed in a systematic review . It should be clear that this variability greatly affects correct dosing.…”

Section: Pharmacological Agentsmentioning

confidence: 79%

Pharmacological sedation management in the paediatric intensive care unit

Baarslag

Allegaert

Knibbe

et al. 2016

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

The population in question is very heterogeneous and this overview can aid clinicians and researchers in moving from practice-based sedation management towards more evidence- or model-based practice. Still, paediatric sedation management can be improved in other ways than pharmacology only, so future research should aim on sedation assessment and implementation strategies of protocolized sedation as well.

show abstract

“…However, sedative drugs sometimes have several undesirable effects, including respiratory depression, hypotension, seizure-like activity, and paradoxical reactions [18,19]. Moreover, it is difficult to determine the effective dosage because children have a narrow safety margin and a large variation among sedative drugs [6]. According to previous studies, a combined therapy with nonpharmacological and pharmacological interventions was more effective than medication alone [8,10].…”

Section: Discussionmentioning

confidence: 99%

“…Third, parents should also wear surgical suits, which may be not effective in reducing children's anxiety. The use of sedative drugs can be an effective way to reduce children's anxiety, but it is difficult to determine the effective dosage because children have a narrow safety margin and a large variation among sedative drugs [6]. Thus, several studies have been conducted to reduce anxiety in children by nonpharmacological methods.…”

Section: Introductionmentioning

confidence: 99%

Effect of transportation method on preoperative anxiety in children: a randomized controlled trial

Park

Lee

et al. 2020

Korean J Anesthesiol

View full text Add to dashboard Cite

Background:This study was performed to evaluate the effect of a wagon as a transport vehicle instead of the standard stretcher car to reduce children's anxiety of separation from parents. The secondary goal was to evaluate whether this anxiolytic effect was related to age. Methods: We divided 80 children (age 2-7 years) into two groups. The stretcher group was transferred to the operating room on a conventional stretcher car, whereas the wagon group was transferred using a wagon. The level of anxiety was evaluated three times using the Modified Yale Preoperative Anxiety Scale (mYPAS): in the waiting area (T0), in the hallway to the operating room (T1), and before induction of anesthesia (T2). Results: The mYPAS score was significantly lower in the wagon group (36.7 [31.7, 51.7]) than in the stretcher group (51.7 [36.7, 83.3]) at T1 (P = 0.007). However, there was no difference in the mYPAS score between the two groups at T2 (46.7 [32.5, 54.2] vs. 51.7 [36.7, 75.0], respectively, P = 0.057). The baseline anxiety tended to be lower with increasing age (r = −0.248, P = 0.031). During transportation to the operating room, the increase in the mYPAS score (T1-T0) was greater as the age of children decreased in the stretcher group (r = −0.340, P = 0.034). However, no correlation was observed in the wagon group (r = −0.053, P = 0.756). Conclusions:The wagon method decreased preoperative anxiety, suggesting that it may be a good alternative for reducing preoperative anxiety in children.

show abstract

Inter-individual variation in midazolam clearance in children

Cited by 23 publications

References 47 publications

Predicting CYP3A‐mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure

Predicting CYP3A‐mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure

Pharmacological sedation management in the paediatric intensive care unit

Effect of transportation method on preoperative anxiety in children: a randomized controlled trial

Contact Info

Product

Resources

About