Oral Melatonin in Critically Ill High-risk Patients
Condition: Critically Ill Patients; Mechanically Ventilated Patients
MeSH terms: Critical Illness
Study type: Interventional
Phase: Phase 4

Summary: 
      Sleep disruptions are extremely common in high-risk critically ill patients. The
      investigators want to analyse oral melatonin potentialities as a sedative and a free-radicals
      scavenger for critically ill patients, and secondarily for preventing Delirium during their
      ICU stay and post-traumatic stress disorders after ICU discharge.
    

Detailed description: 
      The physiological secretion of such melatonin follows a circadian rhythm: melatonin plasma
      concentration increases with the dark reaching a peak around to midnight and then gradually
      decreases (Reiter, 1996; Shigeta et al., 2001; Kunz et al., 2004; Brzezinski et al., 2005).

      Administration of oral melatonin could be useful in critically ill high-risk patients in
      Intensive Care Units because these patients are often suffering from sleep disturbances
      (Weber et al., 1985; Bourne and Mills, 2004) possibly because of:

        -  presence of underlying pathology with pain and anxiety,

        -  presence of oral or nasal respiratory prosthesis,

        -  execution of therapeutic procedures on 24 h. Moreover it has been demonstrated that in
           ICU patients melatonin rhythm is desynchronized (Bourne and Mills, 2000). This is
           probably related to sedation and-or mechanical ventilation. Furthermore, it has been
           showed that melatonin is a powerful anti-oxidant, therefore it could be potentially
           useful in critical patients usually characterized by increased production of oxygen free
           radicals.

      AIM OF THE STUDY The study is aimed to estimate if the administration of oral melatonin in
      ICU patients is able to regularize the sleep-waking rhythm, improving sleep quality and
      reducing episodes of agitation/mental confusion. The main objectives are: assessment of sleep
      quality, prevalence of mental confusion/agitation, amount of daily sedative drugs
      administered and modification of redox status.

      ENROLLMENT OF PATIENTS At the admission in ICU, obtained the informed consent, the patients
      will be randomly assigned to the "Treatment" group receiving melatonin 3mg BID by oral route
      (or nasogastric tube) or to the "Control" group receiving placebo. The sedation will be
      performed according to clinical standard.

      EXPERIMENTAL PROTOCOLS

      The following parameters will be monitored:

        -  epidemiological data,

        -  quality of the sleep estimated by wrist actigraphy,

        -  EEG profile on 24h in order to estimate the distribution of sleep phases,

        -  diurnal and nocturnal hours of sleep,

        -  total amount of sedative drugs during 24 hours, particularly during nocturnal sedation,

        -  assessment of sedation level (RASS) (Sessler et al., 2002; Ely et al., 2003),

        -  episodes of psychomotor agitation and mental confusion (CAM-ICU) (Ely, 2001; 2004),

        -  evaluation of blood redox state (GSH, GSSG, GSH/GSSG),

        -  adverse events.

      AT THE DISCHARGE FROM ICU, evaluation of:

        -  SCID-I and SCID-II (Structured Clinical Interview for DSM),

        -  CAPS (Clinician Administered PTSD Scales),

        -  HAM-A and HAM-D (Hamilton Rating Scales for Anxiety and for Depression),

        -  completion of the module for the stressors in ICU and for the transcription of the
           dreams.

           3 MONTHS AFTER DISCHARGE FROM ICU, evaluation of:

        -  SCID-I and II,

        -  CAPS,

        -  HAM-A and HAM-D,

        -  TAT (Thematic Apperception Test),

        -  completion of the module for the stressors in ICU and for the transcription of the
           dreams.
    

Intervention name(s): Oral melatonin 3mg BID; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Identical tablets containing melatonin 3 mg. Nurses are requested to give two tablets daily, at 8 PM and 12 PM; Identical tablets without the active principles. Each evening nurses are requested to give 2 tablets at 8 PM and 12 PM
Other intervention name(s): MELATONIN 3 mg
Intervention MeSH terms: Melatonin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: melatonin; actigraphy; sedation; critical patients; ICU