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.
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References
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
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
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
Maestroni GJ (1996) Melatonin as a therapeutic agent in experimental endotoxic shock. J Pineal Res 20:84–89
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
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
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
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
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
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
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
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
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
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
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
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
Lewy AJ, Wehr TA, Goodwin FK, Newsome DA, Markey SP (1980) Light suppresses melatonin secretion in humans. Science 210:1267–1269
Brzezinski A (1997) Mechanisms of disease: melatonin in humans. N Engl J Med 336:186–195
Perras B, Meier M, Dodt C (2006) Light and darkness do not regulate melatonin secretion in critically ill patients. Intensivmedizin 43:I54
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
Srinivasan V, Maestroni G, Cardinali D, Esquifino A, Perumal SP, Miller S (2005) Melatonin, immune function and aging. Immunol Ageing 2:17
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
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
Moreno R, Morais P (1997) Validation of the simplified therapeutic intervention scoring system on an independent database. Intensive Care Med 23:640–644
Keene AR, Cullen DJ (1983) Therapeutic Intervention Scoring System: update 1983. Crit Care Med 11:1–3
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
Bourne RS, Mills GH (2006) Melatonin: possible implications for the postoperative and critically ill patient. Intensive Care Med 32:371–379
McIntyre IM, Norman TR, Burrows GD, Armstrong SM (1989) Human melatonin suppression by light is intensity dependent. J Pineal Res 6:149–156
McIntyre IM, Norman TR, Burrows GD, Armstrong SM (1989) Human melatonin response to light at different times of the night. Psychoneuroendocrinology 14:187–193
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
Van den Berghe G (2002) Dynamic neuroendocrine responses to critical illness. Front Neuroendocrinol 23:370–391
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.
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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
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DOI: https://doi.org/10.1007/s00134-007-0769-x