INTRODUCTION: Sedation is an essential part of paediatric critical care. Midazolam, often in combination with opioids, is the current gold standard drug. However, as it is a far-from-ideal agent, clonidine is increasingly being used in children. This drug is prescribed off-label for this indication, as many drugs in paediatrics are. Therefore, the CLOSED trial aims to provide data on the pharmacokinetics, safety and efficacy of clonidine for the sedation of mechanically ventilated patients in order to obtain a paediatric-use marketing authorisation. METHODS AND ANALYSIS: The CLOSED study is a multicentre, double-blind, randomised, active-controlled non-inferiority trial with a 1:1 randomisation between clonidine and midazolam. Both treatment groups are stratified according to age in three groups with the same size: <28 days (n=100), 28 days to <2 years (n=100) and 2-18 years (n=100). The primary end point is defined as the occurrence of sedation failure within the study period. Secondary end points include a pharmacokinetic/pharmacodynamic relationship, pharmacogenetics, occurrence of delirium and withdrawal syndrome, opioid consumption and neurodevelopment in the neonatal age group. Logistic regression will be used for the primary end point, appropriate statistics will be used for the secondary end points. ETHICS: Written informed consent will be obtained from the parents/caregivers. Verbal or deferred consent will be used in the sites where national legislation allows. The study has institutional review board approval at recruiting sites. The results will be published in a peer-reviewed journal and shared with the worldwide medical community. TRIAL REGISTRATION: EudraCT: 2014-003582-24; Clinicaltrials.gov: NCT02509273; pre-results.

• Klíčová slova
• children, criticalillness, paediatrics, pharmacology, sedation,
• MeSH
• abstinenční syndrom MeSH
• clonidin škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• delirium chemicky indukované   MeSH
• dítě MeSH
• hypnotika a sedativa škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• jednotky intenzivní péče MeSH
• kojenec MeSH
• lidé MeSH
• midazolam škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• mladiství MeSH
• neúspěšná terapie MeSH
• novorozenec MeSH
• opioidní analgetika aplikace a dávkování   MeSH
• předškolní dítě MeSH
• umělé dýchání MeSH
• vývoj dítěte účinky léků   MeSH
• výzkumný projekt * MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• clonidin MeSH
• hypnotika a sedativa MeSH
• midazolam MeSH
• opioidní analgetika MeSH

BACKGROUND: This position statement provides clinical recommendations for the assessment of pain, level of sedation, iatrogenic withdrawal syndrome and delirium in critically ill infants and children. Admission to a neonatal or paediatric intensive care unit (NICU, PICU) exposes a child to a series of painful and stressful events. Accurate assessment of the presence of pain and non-pain-related distress (adequacy of sedation, iatrogenic withdrawal syndrome and delirium) is essential to good clinical management and to monitoring the effectiveness of interventions to relieve or prevent pain and distress in the individual patient. METHODS: A multidisciplinary group of experts was recruited from the members of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC). The group formulated clinical questions regarding assessment of pain and non-pain-related distress in critically ill and nonverbal children, and searched the PubMed/Medline, CINAHL and Embase databases for studies describing the psychometric properties of assessment instruments. Furthermore, level of evidence of selected studies was assigned and recommendations were formulated, and grade or recommendations were added on the basis of the level of evidence. RESULTS: An ESPNIC position statement was drafted which provides clinical recommendations on assessment of pain (n = 5), distress and/or level of sedation (n = 4), iatrogenic withdrawal syndrome (n = 3) and delirium (n = 3). These recommendations were based on the available evidence and consensus amongst the experts and other members of ESPNIC. CONCLUSIONS: This multidisciplinary ESPNIC position statement guides professionals in the assessment and reassessment of the effectiveness of treatment interventions for pain, distress, inadequate sedation, withdrawal syndrome and delirium.

• Klíčová slova
• Assessment, Delirium, Distress, Pain, Sedation, Withdrawal syndrome,
• MeSH
• abstinenční syndrom diagnóza   terapie   MeSH
• delirium diagnóza   terapie   MeSH
• dítě MeSH
• hypnotika a sedativa terapeutické užití   MeSH
• jednotky intenzivní péče normy   MeSH
• kojenec MeSH
• konsensus MeSH
• kritický stav * MeSH
• lidé MeSH
• management bolesti metody   MeSH
• měření bolesti metody   MeSH
• novorozenec MeSH
• pooperační delirium diagnóza   terapie   MeSH
• předškolní dítě MeSH
• psychický stres MeSH
• psychomotorický neklid diagnóza   farmakoterapie   MeSH
• směrnice pro lékařskou praxi jako téma * MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• hypnotika a sedativa MeSH