Dexmedetomidine for Prolonged Sedation in PICUs

NCT03760978 | Completed

• 1 other identifier: 4466/AO/18; AOP1403
• Study Type: observational
• Target: 163
• Locations: 1 country
• Sites: 9

Brief Summary

Sedation management of the critically ill patients is still a challenge for the pediatric intensivists. Worldwide the most common sedation approach includes the concomitant use of opioids and benzodiazepines. The use of these drugs is associated with adverse events contributing with morbidity, such as decreased spontaneous ventilation, withdrawal syndrome and delirium onset. Moreover, benzodiazepine demonstrated a neurotoxic apoptotic effect that could potentially impact neurocognitive outcome. Dexmedetomidine (DEX) is a selective alpha-2-adrenergic agonist with sedative, analgesic and anxiolytic effects. Its unique pharmacological profile allows reaching a conscious sedation state with minimal respiratory depression, promoting faster ventilation weaning and better collaboration with the medical staff. Moreover, DEX seems to present adjuvant properties towards withdrawal syndrome and delirium. Finally, some studies in animals suggested that Dexmedetomidine might have a role of neuro-protection, especially in a contest of cerebral ischemia. Currently, the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved DEX only for the adult population and for sedation lasting not more than 24 hours. The Italian Medicines Agency (AIFA), in January 2016, approve DEX in children for specific indications including difficult sedation in mechanically ventilated critically ill patients. Up to now, few data are still available regarding its efficacy and safety for prolonged sedation in Pediatric Intensive Care Units (PICUs) and no studies have reported the use of DEX after AIFA's approval so far. Aims of the study are: to evaluate the characteristics of DEX use for prolonged sedation ≥24 hours in critically ill children (indication, dosages, time of infusion, time of infusion weaning, association with other drugs); to evaluate its efficacy in terms of comfort and conventional drug sparing, using standardized and validate measures; further, to evaluate its efficacy in terms of reduction of incidence of withdrawal syndrome and delirium; to evaluate its safety profile collecting any adverse event potentially correlated with its administration; to define if efficacy and safety could differ among approved indications versus not-approved ones. Design: Multicenter observational prospective study, involving tertiary-care PICUs. Study period: From January 2016 up to reaching of the calculated sample size (N patients =163). Population: All critically ill patients \<18 years who received prolonged sedation including DEX for ≥24 hours. In case of multiple infusions, only data regarding the first infusion will be included. Exclusion criteria: extreme prematurity (\<28 weeks of gestational age), hypersensitivity to the active substance, incomplete data form. . Collecting data strategy: Data will be prospectively collected from each Institution by means of a anonymous standardized form completed by two different investigators per center. For each patient, the following variables will be collected: demographics characteristics (age, gender, race, weight) and clinical features (main diagnosis, associated morbidities, PIM3 score ad admission, number of high intensity interventions during PICU-stay, mechanical ventilation features, inotropic drugs use, length of stay, survival at discharge); DEX administration characteristics (indication, loading dose, minimum and maximum dosages, duration of DEX infusion, duration of DEX infusion weaning) and information on concomitant use of analgesics or sedative drugs (name of drugs and respective dosages at DEX starting time and 24 hours later); clinical scores of analgesia and sedation (Comfort Behavior Scale, CBS), withdrawal syndrome (Withdrawal Assessment Toll-1, WAT-1) and delirium (Cornell Assessment of Pediatric Delirium, CAPD) depending on the respective indication, registered immediate pre-DEX and 24 hours later; any adverse event potentially related to DEX administration and any related intervention, if present. In particular, we the investigators evaluate if bradycardia, hypotension (with or without poor perfusion), hypertension, agitations or other events are registered during the infusion. Further, investigators will register if any sign of DEX withdrawal (tachycardia, hypertension, agitation, other) are present immediately after the infusion. Statistical analysis: Descriptive and analytic statistics will be performed according with the variable characteristics. A causal multivariate model will be developed to identify any significant risk or protective factors towards adverse outcomes (ineffective sedation, onset of adverse events).

Conditions

Prolonged Sedation

Keywords

sedation; dexmedetomidine

Outcome Measures

Primary Outcomes (1)

• Comfort Behavior Scale (CBS)

  Standardized validated score for sedation level and pain assessment; range 6-30; lower values represent a deep level of sedation

  Immediately before DEX start and 24 hours later

Secondary Outcomes (1)

• Opioid and benzodiazepines dosage

  Immediately before DEX start and 24 hours later.

Other Outcomes (3)

• Withdrawal Assessment Tool-1

  Immediately before DEX start and 24 hours later.

• Cornell Assessment of Pediatric Delirium, CAPD

  Immediately before DEX start and 24 hours later

• Onset of adverse events

  During and immediately after dexmedetomidine infusion.

Study Arms (1)

dex group

Critically ill patients \<18 year-old receiving prolonged sedation with endovenous dexmedetomidine (dosage 0.2 mcg/Kg/hour to 1.8 mcg/Kg/hour) more than 24 hours

Drug: Dexmedetomidine

Interventions

Dexmedetomidine DRUG

Also known as: dexdor, precedex

dex group

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Critically ill children admitted to PICU

You may qualify if:

• age \<18 years
• admission to PICU
• sedation with dexmedetomidine lasted more than 24 hours
• written informed consent

You may not qualify if:

• extreme prematurity (\<28 weeks of gestational age)
• hypersensitivity to the active substance
• incomplete data regarding outcome measures

Sponsors & Collaborators

• Azienda Ospedaliera di Padova: lead
• IRCCS Azienda Ospedaliero-Universitaria di Bologna: collaborator

Study Sites (9)

Pediatric Intensive Care Unit, Children's Hospital C.Arrigo, Alessandria, Italy

Alessandria, Italy

Location

Pediatric Intensive Care Unit, ASST John XXIII Pope Hospital, Bergamo, Italy

Bergamo, Italy

Location

Pediatric Intensive Care Unit, S.Orsola Malpighi Hospital, University of Bologna, Italy

Bologna, Italy

Location

Pediatric Intensive Care Unit, Children's Hospital V.Buzzi, Milan, Italy

Milan, Italy

Location

Pediatric and Neonatal Intensive Care Unit, Maggiore della Carità Hospital, Novara, Italy

Novara, Italy

Location

Terapia Intensiva Pediatrica Azienda Ospedaliera di Padova

Padua, 35127, Italy

Location

Pediatric Intensive Care Unit, Bambino Gesù Children's Hospital, Rome, Italy

Roma, Italy

Location

Pediatric Intensive Care Unit, A.Gemelli Hospital, Sacro Cuore Catholic University, Rome Italy

Rome, Italy

Location

Pediatric Intensive Care Unit, Burlo Garofalo Hospital, University of Trieste, Italy

Trieste, Italy

Location

Related Publications (6)

• Mondardini MC, Astuto M, Amigoni A. Inclusion of dexmedetomidine for pediatric indications in the list of medicinal products issued by the National Law 648/96. Minerva Anestesiol. 2017 Aug;83(8):891-892. doi: 10.23736/S0375-9393.17.11975-9. Epub 2017 Mar 3. No abstract available.

  PMID: 28256816 RESULT

• Romagnoli S, Amigoni A, Blangetti I, Casella G, Chelazzi C, Forfori F, Garisto C, Mondardini MC, Moltrasio M, Pasero D, Principi T, Ricci Z, Tarantino F, Conti G. Light sedation with dexmedetomidine: a practical approach for the intensivist in different ICU patients. Minerva Anestesiol. 2018 Jun;84(6):731-746. doi: 10.23736/S0375-9393.18.12350-9. Epub 2018 Feb 5.

  PMID: 29405671 RESULT

• Sperotto F, Mondardini MC, Vitale F, Daverio M, Campagnano E, Ferrero F, Rossetti E, Vasile B, Dusio MP, Ferrario S, Savron F, Brugnaro L, Amigoni A; Pediatric Neurological Protection and Drugs (PeNPAD) Study Group. Prolonged sedation in critically ill children: is dexmedetomidine a safe option for younger age? An off-label experience. Minerva Anestesiol. 2019 Feb;85(2):164-172. doi: 10.23736/S0375-9393.18.13062-8. Epub 2018 Oct 30.

  PMID: 30394067 RESULT

• Grant MJ, Schneider JB, Asaro LA, Dodson BL, Hall BA, Simone SL, Cowl AS, Munkwitz MM, Wypij D, Curley MA; Randomized Evaluation of Sedation Titration for Respiratory Failure Study Investigators. Dexmedetomidine Use in Critically Ill Children With Acute Respiratory Failure. Pediatr Crit Care Med. 2016 Dec;17(12):1131-1141. doi: 10.1097/PCC.0000000000000941.

  PMID: 27654816 RESULT

• Tabacco B, Tacconi C, Amigoni A. Survey on monitoring analgesia and sedation in the Italian Pediatric Intensive Care Units. Minerva Anestesiol. 2017 Oct;83(10):1010-1016. doi: 10.23736/S0375-9393.17.11707-4. Epub 2017 Mar 28.

  PMID: 28358177 RESULT

• Mason KP, Lerman J. Review article: Dexmedetomidine in children: current knowledge and future applications. Anesth Analg. 2011 Nov;113(5):1129-42. doi: 10.1213/ANE.0b013e31822b8629. Epub 2011 Aug 4.

  PMID: 21821507 RESULT

Related Links

• see Group of Study PeNPAD (Italian Research Group on Pediatric Neurological Protection and Drugs)

MeSH Terms

Interventions

Dexmedetomidine

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• angela amigoni, MD

  Azienda Ospedaliera di Padova

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 29, 2018
• First Posted: December 3, 2018
• Study Start: January 1, 2016
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2018
• Last Updated: January 23, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (9)