European Journal of Pediatrics

, Volume 177, Issue 9, pp 1363–1366 | Cite as

Correction to: Melatonin as an alternative sedation method during magnetic resonance imaging in preschool children with musculoskeletal problems

  • Agneza Marija Pasini
  • Josip Marjanović
  • Goran Roić
  • Nikola Dukarić
  • Ana Tripalo Batoš
  • Zoran Bahtijarević
  • Alenka GagroEmail author


MRI Sedation Melatonin Juvenile idiopathic arthritis 



general anesthesia


juvenile idiopathic arthritis


magnetic resonance imaging


MRI is an important diagnostic tool in pediatric rheumatology, enabling early detection of synovial membrane inflammation and bone marrow edema, findings that precede joint erosions [2]. As excessive motion in the MRI scanner hinder the accurate diagnosis, the examinees are required to lay still, which is difficult for preschool children due to the claustrophobic environment, acoustic noise and the length of the exam. To avoid motion artifacts, sedation or general anesthesia are commonly used. These interventions in children have a well described risk and also and incur substantial costs. Melatonin, a natural sleep cycle regulator that can induce sleep in children when administered orally, is discussed for over 10 years as an attractive alternative to conventional sedation due to its low cost and excellent safety profile. We wanted to examine whether the level of sedation with melatonin is adequate to perform a successful MRI scan of joints in order to avoid sedation/GA and thus reduce health costs and waiting lists.

Materials and methods

The study population was comprised of 15 children (median age = 4.5 years) with suspicion for juvenile idiopathic arthritis (JIA) and indication for joint MRI under sedation/GA. All children were prescribed prolonged-release melatonin product available in the Croatia and licensed for patients with primary insomnia aged 55 and over. A drug informed consent with parenteral information of off-label use was sought before administration. Melatonin was dispensed from pharmacy in a tablet. These tablets were crushed in order to enable the release profile like that of an immediate release preparation.

The study was done in the morning between 8 and 10 a.m.; parents were instructed to wake up the children an hour earlier than usual, and keep them awake until the MRI. Parents were asked about the amount of sleep prior to the examination and children slept 8–9 h during the night. An IV access for MRI contrast material was established in all the children upon arrival. Thirty minutes before the MRI 10 mg of melatonin added to a milk drink was administered to a child orally. We decided to administer the dose of 10 mg because it has been shown in previous studies to be safe (without risk of respiratory compromise) and to have good sedative effect [5].

Mixing melatonin with milk was shown not to compromise the integrity of the drug and thus ensure delivery of the prescribed dose [9]. All children were placed in the darkened room in the close proximity to MRI room and they were accompanied by parents during preparation for MRI as well as during the scan. The average duration of imaging was 30 min. Awakening occurred spontaneously upon exiting the MRI machine in all the patients.


We performed a total of 16 joint MRIs in 15 patients with suspected JIA. All children had non-steroidal anti-inflammatory agent in therapy. Adequate levels of sedation, allowing successful completion of the joint MRI, were achieved in 14/15 patients. Sedation level was assessed using University of Michigan sedation scale (MSS) [7]. Children were considered ready for scanning when they achieved level 3 (deeply sedated: deeply asleep and rousable to significant physical stimulation but settles soon afterwards) [10].

One patient had two MRI exams for different joints. The first one was successful, but the second one was ineffective (Table 1, Fig. 1). The quality of structural MRI scans was rated according to a five-point rating scale by an experienced radiologist as 1: no motion artifacts, excellent quality, 2: little motion artifacts, good quality, 3: moderate motion artifacts, acceptable quality, 4: excessive motion artifacts, poor quality, and 5: incomplete scan. Scans of score 1–3 were considered to be of sufficient quality for diagnostic purposes. In our sample, 15/16 had scans of good to excellent quality (score 1–2). One patient had ineffective MRI scan (score 4) [3].
Table 1

Patient medical reports

Age (yr) [mean (range)]

4,5 (3–6)

Weight (kg) [mean (range)]

19,4 (15–24)

I.V. cannula inserted


Time from administration to scan (min) [range]


Scan length (min)


Achieved deep sedation (Michigan Sedation Scale (MSS) 3)


Failed to reach deep sedation (MSS 0–1)


Fig. 1

One of our patients who achieved good level of sedation and afterwards had excellent quality of pre- and post-contrast enchanced knee MRI scans (a, b), and our patient with ineffective sedation and thus poor quality knee MRI scan (c)

As in other studies no adverse effects from the sigle administration of melatonin were encountered [5]. We didn’t observe any respiratory compromise or allergic reactions in the period immediately after the administration of melatonin, and soon after the scanning. In the follow-up period of one year, parents did not report any safety issues (previously explained and written in an informed consent) which regard to melatonin administration.


Sedation/GA is not always successful in preventing the motion artifacts, which can lead to repeated examinations, negative psychologic impact on the child and the family, prolonged hospital stay and significant increase in cost [1]. In prospective study on 1062 children who underwent MRI or CT, Malviya et al. reported excessive motion in 12% of scans of sedated children and 0.7% of those completed with general anaesthesia [6]. To avoid the use of sedation and general anesthesia with pediatric MRI, alternative methods such as use of pacifiers, swaddling, sleep deprivation, explaining the procedure of the MRI investigation using photos or a video, using a small model of the MRI scanner to familiarize the child with the layout of the unit and mock scanner training protocol, melatonin or hypnosis have been explored [3, 4]. Melatonin, owing to its role in circadian rhythm regulation, is a sedative, anxiolytic and hypnotic agent with excellent safety profile, therefore suitable for premedication before general anesthesia, or as an alternative sedation method prior to diagnostic (i.e. audiography, MRI and EEG) or therapeutic interventions (i.e dental procedures) [8]. A previous prospective study in an unselected group of 40 children found that melatonin was an effective pre-MRI sedation method in 55% of 40 children with developmental or behavioral problems, with further increase to 76% when used after sleep deprivation [5]. The higher rate of success of melatonin administration in our study could be explained by the lack of other comorbidities that might influence the compliance. Furthermore, in order to alleviate anxiety and reduce movement during the examination all patients and parents/guardians were familiarized with the examination prior to the scan explaining the procedure of the MRI investigation using photos and by the presence of an adult family member or guardian with the child prior to and during the scan. All children included in our study had an intravenous cannula inserted in order to give them gadolinium DTPA contrast. In order to avoid additional disturbance of children this procedure was done at least one hour before MRI examination. This time delay in our experience was sufficient in order to alleviate the distress in our patients so we advocate this approach in children. Sleep deprivation can reduce the need for sedation in young children and infants undergoing MRI examination [4]. Since musculoskeletal MRI examination in our study was performed in children as outpatient examination, we used no sleep deprivation in order to avoid the possible differences among children related to the compliance and cooperation of parents/guardians.

In summary, our study provides additional evidence for the effectiveness and safety of melatonin as a sedation method before the musculoskeletal MRI. Unlike in the previous studies, our patients all had newly established IV access, and this painful intervention did not interfere with the sedative effect of melatonin. A potential shortcoming of our study is the small sample size and use of MRI to image the joints, which are easier to immobilize than the other body parts. Although a direct comparison between melatonin and standard sedation/GA in a larger cohort of patient is needed to draw the final conclusion, the use of melatonin in our group of patients with musculoskeletal problems did have good sedative effect and we could get satisfactory MRI images suitable for interpretation. Thereby we managed to reduce health costs and prevent possible adverse events if using standard sedation/GA techniques. In conclusion, our rate of success may be due to the combination of the dose of melatonin, our training protocol, and lack of behavioral problems and comorbidities in the studied population.


Authors’ contributions

Dr. Pasini conceptualized and drafted the initial manuscript, approved the final manuscript.

Dr. Marjanović helped with the radiologic procedures and findings and making the diagnosis, writing the initial manuscript and critically revised the manuscript.

Dr. Roić helped with the radiologic procedures and findings and making the diagnosis, writing the initial manuscript and critically revised the manuscript.

Dr. Dukarić helped with the radiologic procedures and findings and making the diagnosis, writing the initial manuscript.

Dr. Tripalo Batoš helped with the radiologic findings and making the diagnosis, writing the initial manuscript.

Dr. Bahtijarević was involved in the making the diagnosis, follow-up of the patient and writing the initial manuscript.

Dr. Gagro conceptualized initial manuscript, critically revised the manuscript, approved the final manuscript.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Compliance with Ethical Standards

An informed consent with parenteral information of off-label use was obtained.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Arlachov Y, Ganatra RH (2012) Sedation/anaesthesia in paediatric radiology. Br J Radiol 85(1019):e1018–e1031. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Colebatch-Bourn AN, Edwards CJ, Collado P, D'Agostino MA, Hemke R, Jousse-Joulin S, Maas M, Martini A, Naredo E, Østergaard M et al (2015) EULAR-PReS points to consider for the use of imaging in the diagnosis and management of juvenile idiopathic arthritis in clinical practice. Ann Rheum Dis 74(11):1946–1957. CrossRefPubMedGoogle Scholar
  3. 3.
    de Bie HM, Boersma M, Wattjes MP, Adriaanse S, Vermeulen RJ, Oostrom KJ, Huisman J, Veltman DJ (2010) Delemarre-Van de Waal HA. Preparing children with a mock scanner training protocol results in high quality structural and functional MRI scans. Eur J Pediatr 169(9):1079–1085. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Edwards AD, Arthurs OJ (2011) Paediatric MRI under sedation: is it necessary? What is the evidence for the alternatives? Pediatr Radiol 41(11):1353–1364. CrossRefPubMedGoogle Scholar
  5. 5.
    Johnson K, Page A, Williams H, Wassemer E, Whitehouse W (2002) The use of melatonin as an alternative to sedation in uncooperative children undergoing an MRI examination. Clin Radiol 57(6):502–506CrossRefPubMedGoogle Scholar
  6. 6.
    Malviya S, Voepel-Lewis T, Eldevik OP, Rockwell DT, Wong JH, Tait AR. Sedation and general anaesthesia in children undergoing MRI and CT: adverse events and outcomes. Br J Anaesth 200084(6):743–748Google Scholar
  7. 7.
    Malviya S, Voepel-Lewis T, Tait AR, Merkel S, Tremper K, Naughton N (2002) Depth of sedation in children undergoing computed tomography: validity and reliability of the University of Michigan Sedation Scale (UMSS). Br J Anaesth 88(2):241–245CrossRefPubMedGoogle Scholar
  8. 8.
    Sánchez-Barceló EJ, Mediavilla MD, Reiter RJ (2011) Clinical uses of melatonin in pediatrics. Int J Pediatr 2011:892624. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Shah T, Tse A, Gill H, Wong I, Sutcliffe A, Gringras P, Appleton R, Tuleu C (2008) Administration of melatonin mixed with soft food and liquids for children with neurodevelopmental difficulties. Dev Med Child Neurol. 50(11):845–849. CrossRefPubMedGoogle Scholar
  10. 10.
    Sury MR, Fairweather K (2006) The effect of melatonin on sedation of children undergoing magnetic resonance imaging. Br J Anaesth 97(2):220–225CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Agneza Marija Pasini
    • 1
  • Josip Marjanović
    • 2
  • Goran Roić
    • 1
  • Nikola Dukarić
    • 1
  • Ana Tripalo Batoš
    • 1
  • Zoran Bahtijarević
    • 1
  • Alenka Gagro
    • 1
    • 3
    • 4
    Email author
  1. 1.Children’s Hospital Zagreb, School of MedicineUniversity of ZagrebZagrebCroatia
  2. 2.Faculty of Medicine, Josip Juraj StrossmayerUniversity of OsijekOsijekCroatia
  3. 3.Department of RadiologyRoyal Belfast Hospital for Sick ChildrenBelfastUK
  4. 4.Department of Pulmonology, Allergology, Immunology and Rheumatology, Department of PediatricsChildren’s Hospital ZagrebZagrebCroatia

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