Dexmedetomidine Pharmacokinetics-pharmacodynamics in Mechanically Ventilated Children With Single-organ Respiratory Failure
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ClinicalTrials.gov Identifier: NCT01076816
Recruitment Status :
(Poor inclusion rate.)
Currently, dexmedetomidine is approved by the United States Food and Drug Administration (FDA) for short-term analgosedation (<24h) in mechanically-ventilated critical care adult patients and sedation of non-intubated adult patients prior to and/or during surgical and other procedures. Trials are underway to investigate its pharmacokinetics, clinical efficacy and safety in long-term use. Clinical experience with dexmedetomidine in the paediatric population is limited. Moreover, during childhood many developmental changes take place with consequences on drug exposure and drug response. Finally, critical illness itself can affect drug pharmacokinetics and -dynamics. Therefore, we cannot simply extrapolate adult data for use in children but we are in need of data on pharmacokinetics and pharmacodynamics in every paediatric subpopulation.
dexmedetomidine will be given max 48h. In case analgosedation is still needed after stop of the dexmedetomidine infusion, the treatment is switched to conventional analgosedation regimens.
Additional drugs are given to every inadequately sedated patient (assessed by regular Comfort scoring). In case of oversedation or adverse drug events (hypotension, bradycardia), a downtitration (or stop) of the dexmedetomidine infusion is needed.
Procedure: Vital signs
systolic and diastolic blood pressure, heart rate, respiratory rate,oxygen saturation, temperature are assessed baseline and at least per hour reassessed after starting the dexmedetomidine.
Procedure: blood sampling
Blood sampling for pharmacokinetic modelling is limited to a maximum of 1,8 ml/kg (in line with the EMEA guidelines on maximum blood sampling in children). Pharmacokinetic parameters and influence of covariates on these parameters will be assessed by a population pharmacokinetic approach.
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Layout table for eligibility information
Ages Eligible for Study:
1 Month to 15 Years (Child)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
patients (m/f) admitted to the paediatric intensive care unit
expected to require at least 24h of mechanical ventilation
patient age : 1 month-15 years
patients with single-organ respiratory failure
patients with neurologic conditions that prohibit an evaluation of adequate analgosedation
no arterial catheter in place at inclusion
patients who have received another investigational drug within 30 days
patients on continuous infusion with neuromuscular blockers
patients with a life expectancy <72h
patients with a known allergy to lorazepam, midazolam and/or morphine
hemodynamically unstable patients (Wernovsky index > 16 points) after full fluid replacement with crystalloid
patients with significant renal insufficiency (creatinine plasma level 1 month-5 year : > 1 mg/dl ; 5-10 years : >1.2 mg/dl; > 10 years : > 1.5 mg/dl)
patients with significant hepatic insufficiency (aspartate aminase >950 UI/L and prothrombin time < 60 or INR >1.4)
previous treatment with α2-adrenoreceptor agonist clonidine within 14 days