Skip to main content

Light and darkness fail to regulate melatonin release in critically ill humans

Intensive Care Medicine volume 33, pages 1954–1958 (2007)Cite this article

Abstract

Objective

Pineal dysfunction has been associated with morbidity and mortality in various animal models of severe illness, and low melatonin plasma concentrations have recently been reported in patients on the ICU. However, it is not known whether the physiological response of the pineal gland to light and darkness is preserved in critical illness.

Design and patients

We examined the nocturnal release of melatonin in response to 1 h of darkness followed by 1 h of bright light (> 10,000 lux) in 20 severely ill patients on a medical ICU. Eleven elderly (median age 73 years) and 9 young patients (38 years) were recruited. Melatonin plasma concentrations were measured at 30-min intervals.

Results

In 15 patients melatonin plasma concentration was low and responded to neither darkness nor light. In three elderly and two young patients melatonin plasma concentrations were elevated irrespective of illumination.

Conclusions

The physiological regulation of melatonin secretion by darkness and light is abolished in severely ill patients.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  1. Bonilla E, Valero-Fuenmayor N, Pons H, Chacin-Bonilla L (1997) Melatonin protects mice infected with Venezuelan equine encephalomyelitis virus. Cell Mol Life Sci 53:430–434

    PubMed  Article  CAS  Google Scholar 

  2. Medina S, Valero-Fuenmayor N, Chacin-Bonilla L, Anez F, Giraldoth D, Arias J, Espina G, Achong AY, Bonilla E (1999) Exposure to 2500 lux increases serum melatonin in Venezuelan equine encephalomyelitis. Neurochem Res 24:775–778

    PubMed  Article  CAS  Google Scholar 

  3. Wichmann MW, Haisken JM, Ayala A, Chaudry IH (1996) Melatonin administration following hemorrhagic shock decreases mortality from subsequent septic challenge. J Surg Res 65:109–114

    PubMed  Article  CAS  Google Scholar 

  4. Maestroni GJ (1996) Melatonin as a therapeutic agent in experimental endotoxic shock. J Pineal Res 20:84–89

    PubMed  Article  CAS  Google Scholar 

  5. Escames G, Leon J, Macias M, Khaldy H, Acuna-Castroviejo D (2003) Melatonin counteracts lipopolysaccharide-induced expression and activity of mitochondrial nitric oxide synthase in rats. FASEB J 17:932–934

    PubMed  CAS  Google Scholar 

  6. Wu CC, Chiao CW, Hsiao G, Chen A, Yen MH (2001) Melatonin prevents endotoxin-induced circulatory failure in rats. J Pineal Res 30:147–156

    PubMed  Article  CAS  Google Scholar 

  7. Reynolds FD, Dauchy R, Blask D, Dietz PA, Lynch D, Zuckerman R (2003) The pineal gland hormone melatonin improves survival in a rat model of sepsis/shock induced by zymosan A. Surgery 134:474–479

    PubMed  Article  Google Scholar 

  8. Gitto E, Karbownik M, Reiter RJ, Tan DX, Cuzzocrea S, Chiurazzi P, Cordaro S, Corona G, Trimarchi G, Barberi I (2001) Effects of melatonin treatment in septic newborns. Pediatr Res 50:756–760

    PubMed  Article  CAS  Google Scholar 

  9. Gitto E, Romeo C, Reiter RJ, Impellizzeri P, Pesce S, Basile M, Antonuccio P, Trimarchi G, Gentile C, Barberi I, Zuccarello B (2004) Melatonin reduces oxidative stress in surgical neonates.J Pediatr Surg 39:184–189

    PubMed  Article  CAS  Google Scholar 

  10. Perras B, Kurowski V, Dodt C (2006) Nocturnal melatonin concentration is correlated with illness severity in patients with septic disease. Intensive Care Med 32:624–625

    PubMed  Article  Google Scholar 

  11. Shilo L, Dagan Y, Smorjik Y, Weinberg U, Dolev S, Komptel B, Balaum H, Shenkman L (1999) Patients in the intensive care unit suffer from severe lack of sleep associated with loss of normal melatonin secretion pattern. Am J Med Sci 317:278–281

    PubMed  Article  CAS  Google Scholar 

  12. Mundigler G, Delle-Karth G, Koreny M, Zehetgruber M, Steindl-Munda P, Marktl W, Ferti L, Siostrzonek P (2002) Impaired circadian rhythm of melatonin secretion in sedated critically ill patients with severe sepsis. Crit Care Med 30:536–540

    PubMed  Article  CAS  Google Scholar 

  13. Miyazaki T, Kuwano H, Kato H, Ando H, Kimura H, Inose T, Ohno T, Suzuki M, Nakajima M, Manda R, Fukuchi M, Tsukada K (2003) Correlation between serum melatonin circadian rhythm and intensive care unit psychosis after thoracic esophagectomy. Surgery 133:662–668

    PubMed  Article  Google Scholar 

  14. Frisk U, Olsson J, Nylen P, Hahn RG (2004) Low melatonin excretion during mechanical ventilation in the intensive care unit. Clin Sci (Lond) 107:47–53

    CAS  Article  Google Scholar 

  15. Olofsson K, Alling C, Lundberg D, Malmros C (2004) Abolished circadian rhythm of melatonin secretion in sedated and artificially ventilated intensive care patients. Acta Anaesthesiol Scand 48:679–684

    PubMed  Article  CAS  Google Scholar 

  16. Paparrigopoulos T, Melissaki A, Tsekou H, Efthymiou A, Kribeni G, Baziotis N, Geronikola X (2006) Melatonin secretion after head injury: a pilot study. Brain Inj 20:873–878

    PubMed  Article  Google Scholar 

  17. Lewy AJ, Wehr TA, Goodwin FK, Newsome DA, Markey SP (1980) Light suppresses melatonin secretion in humans. Science 210:1267–1269

    PubMed  Article  CAS  Google Scholar 

  18. Brzezinski A (1997) Mechanisms of disease: melatonin in humans. N Engl J Med 336:186–195

    PubMed  Article  CAS  Google Scholar 

  19. Perras B, Meier M, Dodt C (2006) Light and darkness do not regulate melatonin secretion in critically ill patients. Intensivmedizin 43:I54

    Google Scholar 

  20. Waldhauser F, Weiszenbacher G, Tatzer E, Gisinger B, Waldhauser M, Schemper M, Frisch H (1988) Alterations in nocturnal serum melatonin levels in humans with growth and aging. J Clin Endocrinol Metab 66:648–652

    PubMed  CAS  Article  Google Scholar 

  21. Srinivasan V, Maestroni G, Cardinali D, Esquifino A, Perumal SP, Miller S (2005) Melatonin, immune function and aging. Immunol Ageing 2:17

    Article  CAS  Google Scholar 

  22. Knaus WA, Zimmerman JE, Wagner DP, Draper EA, Lawrence DE (1981) APACHE-acute physiology and chronic health evaluation: a physiologically based classification system. Crit Care Med 9:591–597

    PubMed  CAS  Article  Google Scholar 

  23. Le Gall JR, Lemeshow S, Saulnier F (1993) A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963

    PubMed  Article  Google Scholar 

  24. Moreno R, Morais P (1997) Validation of the simplified therapeutic intervention scoring system on an independent database. Intensive Care Med 23:640–644

    PubMed  Article  CAS  Google Scholar 

  25. Keene AR, Cullen DJ (1983) Therapeutic Intervention Scoring System: update 1983. Crit Care Med 11:1–3

    PubMed  Article  CAS  Google Scholar 

  26. Miranda DR, de Rijk A, Schaufeli W (1996) Simplified Therapeutic Intervention Scoring System: the TISS-28 items-results from a multicenter study. Crit Care Med 24:64–73

    PubMed  Article  CAS  Google Scholar 

  27. Bourne RS, Mills GH (2006) Melatonin: possible implications for the postoperative and critically ill patient. Intensive Care Med 32:371–379

    PubMed  Article  CAS  Google Scholar 

  28. McIntyre IM, Norman TR, Burrows GD, Armstrong SM (1989) Human melatonin suppression by light is intensity dependent. J Pineal Res 6:149–156

    PubMed  Article  CAS  Google Scholar 

  29. McIntyre IM, Norman TR, Burrows GD, Armstrong SM (1989) Human melatonin response to light at different times of the night. Psychoneuroendocrinology 14:187–193

    PubMed  Article  CAS  Google Scholar 

  30. Bergiannaki JD, Soldatos CR, Paparrigopoulos TJ, Syrengelas M, Stefanis CN (1995) Low and high melatonin excretors among healthy individuals. J Pineal Res 18:159–164

    PubMed  Article  CAS  Google Scholar 

  31. Van den Berghe G (2002) Dynamic neuroendocrine responses to critical illness. Front Neuroendocrinol 23:370–391

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Volker Ott, Helge Züllich, and the nursing staff for excellent cooperation and acknowledge gratefully the skillful technical assistance of Heidi Ruf and Ingrid von Lützau.

Author information

Affiliations

  1. Department of Internal Medicine I, University of Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany

    Boris Perras, Markus Meier & Christoph Dodt

Authors
  1. Boris Perras
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Markus Meier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christoph Dodt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Boris Perras.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Perras, B., Meier, M. & Dodt, C. Light and darkness fail to regulate melatonin release in critically ill humans. Intensive Care Med 33, 1954–1958 (2007). https://doi.org/10.1007/s00134-007-0769-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-007-0769-x

Keywords

  • Melatonin
  • Intensive care unit
  • Critical illness
  • Bright light
  • Darkness