Impaired circadian rhythm of melatonin secretion in sedated critically ill patients with severe sepsis*

Mundigler, Gerald; Delle‐Karth, Georg; Koreny, Maria; Zehetgruber, Manfred; Steindl–Munda, Petra; Marktl, Wolfgang; Fertl, Lisa; Siostrzonek, Peter

doi:10.1097/00003246-200203000-00007

Cited by 283 publications

(231 citation statements)

References 37 publications

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“…The central modulation of the immune system and of metabolism is likely to affect the clinical course of sepsis significantly. The septic state includes altered regulation of body temperature, impaired host-defense , abnormal sleep patterns (Mundigler et al, 2002), suppression of appetite (Campbell, 1999), and blunted daily rhythms in behavior and hormonal secretion (Bornstein et al, 1998;Carlson et al, 2006) that are all influenced by the central nervous system.…”

Section: Introductionmentioning

confidence: 99%

Central neural distribution of immunoreactive Fos and CRH in relation to plasma ACTH and corticosterone during sepsis in the rat

Carlson

Chiu

Fiedler

et al. 2007

Experimental Neurology

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Although brain pathways activated by sepsis may respond acutely to endotoxin administration, the long-term central response to sepsis is not known. We prepared male rats for hormonal sampling at the circadian nadir (AM) and peak (PM) after cecal ligation and puncture (CLP) or sham surgery. Diurnal variation of corticosterone was present on postoperative day (D) 3 and D4 after sham surgery but not after CLP. CLP increased Fos immunostaining in the nucleus of tractus solitarius (NTS), ventrolateral medulla, medullary raphe, parabrachial nucleus, hypothalamus, amygdala, bed nucleus of stria terminalis, and preoptic region. Fos responses were generally greatest on D1 but persisted to the AM of D4. The number of Fos-positive cell nuclei in the NTS on D3 and D4 did not differ but had greater variance on D3 than on D4 (P < 0.01) with a divergent response in the PM of D3 that was correlated with plasma ACTH (r = 0.927, P<0.01) but not with corticosterone. CLP increased CRH-staining intensity in the hypothalamic paraventricular neurons uniformly from D1 through D4 (P<0.01). Similar to Fos in NTS, this response was correlated with plasma ACTH (r = 0.738, P<0.05) and adrenal size (r = 0.730, P<0.05) in the PM of D3. Neuronal CRH became detectable after CLP in specific medullary areas on D1 and in the preoptic region on D3 and D4. Thus, the suppression of circadian variation by CLP was associated with central neural responses that increased in relation to plasma ACTH without apparent influence on the release of corticosterone.

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Section: Introductionmentioning

confidence: 99%

Central neural distribution of immunoreactive Fos and CRH in relation to plasma ACTH and corticosterone during sepsis in the rat

Carlson

Chiu

Fiedler

et al. 2007

Experimental Neurology

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“…According to the association between delirium and irregular patterns of melatonin secretion, which has been described by several studies, irregular melatonin secretion could be one of the mechanisms of delirium (10,23,30,31,(50)(51)(52) as well as the presence of sleep deprivation in hospitalized delirious patients at the ICU, as it has been indicated that melatonin and its agonists could be an effective supplement for prevention and management of delirium (38,53,54). Furthermore, several studies have reported the marked improvement of delirium in delirious patients without side effects due to the use of melatonin and ramelteon (6,45,46).…”

Section: Discussionmentioning

confidence: 98%

Are Melatonin and its Agonist the Natural Solution for Prevention of Delirium in Critically Ill Patients? A Review of Current Studies

Aghakouchakzadeh

Izadpanah

Soltani

et al. 2017

Jundishapur J Nat Pharm Prod

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Background: Delirium is a neuropsychiatric syndrome, which is a common complication at the intensive care unit (ICU). Delirium is a risk factor for increased duration of mechanical ventilation and increased time of stay at the ICU and death. Melatonin is a hormone produced and secreted by the pineal gland, that regulates circadian rhythm. The aim of this investigation was to demonstrate the effect of melatonin in controlling and improving delirium.

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“…Circadian rhythm may be suppressed during acute inflammatory illness, as evidenced by suppression of circadian clock genes in peripheral leukocytes for at least 17 hours after inoculation of endotoxin in mice (34). This finding may explain why diurnal variation of melatonin was blunted in ICU patients with sepsis compared with ICU patients without sepsis (35). Furthermore, injection of endotoxin disrupted sleep by decreasing non-REM sleep and doubling the amount of wakefulness during the night (36).…”

Section: Circadian Rhythm and Sepsismentioning

confidence: 99%

Timing Matters: Circadian Rhythm in Sepsis, Obstructive Lung Disease, Obstructive Sleep Apnea, and Cancer

et al. 2016

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Physiological and cellular functions operate in a 24-hour cyclical pattern orchestrated by an endogenous process known as the circadian rhythm. Circadian rhythms represent intrinsic oscillations of biological functions that allow for adaptation to cyclic environmental changes. Key clock genes that affect the persistence and periodicity of circadian rhythms include BMAL1/CLOCK, Period 1, Period 2, and Cryptochrome. Remarkable progress has been made in our understanding of circadian rhythms and their role in common medical conditions. A critical review of the literature supports the association between circadian misalignment and adverse health consequences in sepsis, obstructive lung disease, obstructive sleep apnea, and malignancy. Circadian misalignment plays an important role in these disease processes and can affect disease severity, treatment response, and survivorship. Normal inflammatory response to acute infections, airway resistance, upper airway collapsibility, and mitosis regulation follows a robust circadian pattern. Disruption of normal circadian rhythm at the molecular level affects severity of inflammation in sepsis, contributes to inflammatory responses in obstructive lung diseases, affects apnea length in obstructive sleep apnea, and increases risk for cancer. Chronotherapy is an underused practice of delivering therapy at optimal times to maximize efficacy and minimize toxicity. This approach has been shown to be advantageous in asthma and cancer management. In asthma, appropriate timing of medication administration improves treatment effectiveness. Properly timed chemotherapy may reduce treatment toxicities and maximize efficacy. Future research should focus on circadian rhythm disorders, role of circadian rhythm in other diseases, and modalities to restore and prevent circadian disruption.

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Impaired circadian rhythm of melatonin secretion in sedated critically ill patients with severe sepsis*

Cited by 283 publications

References 37 publications

Central neural distribution of immunoreactive Fos and CRH in relation to plasma ACTH and corticosterone during sepsis in the rat

Central neural distribution of immunoreactive Fos and CRH in relation to plasma ACTH and corticosterone during sepsis in the rat

Are Melatonin and its Agonist the Natural Solution for Prevention of Delirium in Critically Ill Patients? A Review of Current Studies

Timing Matters: Circadian Rhythm in Sepsis, Obstructive Lung Disease, Obstructive Sleep Apnea, and Cancer

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