title: Melatonin reduces the need for sedation in ICU patients: a randomized controlled trial.
abstract: BACKGROUND
  Critically ill patients suffer from physiological sleep deprivation and have reduced blood melatonin levels. This study was designed to determine whether nocturnal melatonin supplementation would reduce the need for sedation in patients with critical illness.
  
  
  METHODS
  A single-center, double-blind randomized placebo-controlled trial was carried out from July 2007 to December 2009, in a mixed medical-surgical Intensive Care Unit of a University hospital, without any form of external funding. Of 1158 patients admitted to ICU and treated with conscious enteral sedation, 82 critically-ill with mechanical ventilation >48 hours and Simplified Acute Physiology Score II>32 points were randomized 1:1 to receive, at eight p.m. and midnight, melatonin (3+3mg) or placebo, from the third ICU day until ICU discharge. Primary outcome was total amount of enteral hydroxyzine administered.
  
  
  RESULTS
  Melatonin treated patients received lower amount of enteral hydroxyzine. Other neurological indicators (amount of some neuroactive drugs, pain, agitation, anxiety, sleep observed by nurses, need for restraints, need for extra sedation, nurse evaluation of sedation adequacy) seemed improved, with reduced cost for neuroactive drugs. Post-traumatic stress disorder prevalence did not differ between groups, nor did ICU or hospital mortality. Study limitations include the differences between groups before intervention, the small sample size, and the single-center observation.
  
  
  CONCLUSIONS
  Long-term enteral melatonin supplementation may result in a decreased need for sedation, with improved neurological indicators and cost reduction. Further multicenter evaluations are required to confirm these results with different sedation protocols.
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy - giovanni.mistraletti@unimi.it.
authors.forename: G
authors.initials: G
authors.lastname: Mistraletti
authors.forename: M
authors.initials: M
authors.lastname: Umbrello
authors.forename: G
authors.initials: G
authors.lastname: Sabbatini
authors.forename: S
authors.initials: S
authors.lastname: Miori
authors.forename: M
authors.initials: M
authors.lastname: Taverna
authors.forename: B
authors.initials: B
authors.lastname: Cerri
authors.forename: E S
authors.initials: ES
authors.lastname: Mantovani
authors.forename: P
authors.initials: P
authors.lastname: Formenti
authors.forename: P
authors.initials: P
authors.lastname: Spanu
authors.forename: A
authors.initials: A
authors.lastname: D'Agostino
authors.forename: S
authors.initials: S
authors.lastname: Salini
authors.forename: A
authors.initials: A
authors.lastname: Morabito
authors.forename: F
authors.initials: F
authors.lastname: Fraschini
authors.forename: R J
authors.initials: RJ
authors.lastname: Reiter
authors.forename: G
authors.initials: G
authors.lastname: Iapichino
mesh_terms: D000368:Aged; D016292:Procedural Sedation / Q000379:methods*; D003422:Critical Care / Q000379:methods*; D016638:Critical Illness; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006919:Hydroxyzine / Q000008:administration & dosage; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D007362:Intensive Care Units; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D008875:Middle Aged; D012121:Respiration, Artificial
chemical_list: D006993:Hypnotics and Sedatives; D006919:Hydroxyzine; D008550:Melatonin