Serum melatonin concentration in critically ill patients randomized to sedation or non-sedation
BACKGROUND: Abolished circadian rhythm is associated with altered cognitive function, delirium, and as a result increased mortality in critically ill patients, especially in those who are mechanically ventilated. The causes are multifactorial, of which changes in circadian rhythmicity may play a role. Melatonin plays a crucial role as part of the circadian and sleep/wake cycle. Whether sedation effects circadian regulation is unknown. Hence, the objective of this study was to evaluate the melatonin concentration in critically ill patients randomized to sedation or non-sedation and to investigate the correlation with delirium.
METHODS: All patients were included and randomized at the intensive care unit at the hospital of southwest Jutland, Denmark. Seventy-nine patients completed the study (41 sedated and 38 non-sedated). S-melatonin was measured 3 times per day, (03.00, 14.00, and 22.00), for 4 consecutive days in total, starting on the second day upon randomization/intubation. The study was conducted as a sub-study to the NON-SEDA study in which one hundred consecutive patients were randomized to sedation or non-sedation with a daily wake-up call (50 in each arm).
PRIMARY OUTCOME: melatonin concentration in sedated vs. non-sedated patients (analyzed using linear regression). Secondary outcome: risk of developing delirium or non-medically induced (NMI) coma in sedated vs. non-sedated patients, assessed by CAM-ICU (Confusion Assessment Method for the Intensive Care Unit) analyzed using logistic regression.
RESULTS: Melatonin concentration was suppressed in sedated patients compared to the non-sedated. All patients experienced an elevated peak melatonin level early on in the course of their critical illness (p = 0.01). The risk of delirium or coma (NMI) was significantly lower in the non-sedated group (OR 0.42 CI 0.27; 0.66 p < 0.0001). No significant relationship between delirium development and suppressed melatonin concentration was established in this study (OR 1.004 p = 0.29 95% CI 0.997; 1.010).
CONCLUSION: Melatonin concentration was suppressed in sedated, critically ill patients, when compared to non-sedated controls and the frequency of delirium was elevated in sedated patients. Trail registration Clinicaltrials.gov (NCT01967680) on October 23, 2013.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Annals of intensive care - 11(2021), 1 vom: 06. März, Seite 40 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Oxlund, Jakob [VerfasserIn] |
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| Links: |
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| Themen: |
Circadian |
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| Anmerkungen: |
Date Revised 12.03.2021 published: Electronic ClinicalTrials.gov: NCT01967680 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1186/s13613-021-00829-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM322349370 |
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| 520 | |a BACKGROUND: Abolished circadian rhythm is associated with altered cognitive function, delirium, and as a result increased mortality in critically ill patients, especially in those who are mechanically ventilated. The causes are multifactorial, of which changes in circadian rhythmicity may play a role. Melatonin plays a crucial role as part of the circadian and sleep/wake cycle. Whether sedation effects circadian regulation is unknown. Hence, the objective of this study was to evaluate the melatonin concentration in critically ill patients randomized to sedation or non-sedation and to investigate the correlation with delirium | ||
| 520 | |a METHODS: All patients were included and randomized at the intensive care unit at the hospital of southwest Jutland, Denmark. Seventy-nine patients completed the study (41 sedated and 38 non-sedated). S-melatonin was measured 3 times per day, (03.00, 14.00, and 22.00), for 4 consecutive days in total, starting on the second day upon randomization/intubation. The study was conducted as a sub-study to the NON-SEDA study in which one hundred consecutive patients were randomized to sedation or non-sedation with a daily wake-up call (50 in each arm) | ||
| 520 | |a PRIMARY OUTCOME: melatonin concentration in sedated vs. non-sedated patients (analyzed using linear regression). Secondary outcome: risk of developing delirium or non-medically induced (NMI) coma in sedated vs. non-sedated patients, assessed by CAM-ICU (Confusion Assessment Method for the Intensive Care Unit) analyzed using logistic regression | ||
| 520 | |a RESULTS: Melatonin concentration was suppressed in sedated patients compared to the non-sedated. All patients experienced an elevated peak melatonin level early on in the course of their critical illness (p = 0.01). The risk of delirium or coma (NMI) was significantly lower in the non-sedated group (OR 0.42 CI 0.27; 0.66 p < 0.0001). No significant relationship between delirium development and suppressed melatonin concentration was established in this study (OR 1.004 p = 0.29 95% CI 0.997; 1.010) | ||
| 520 | |a CONCLUSION: Melatonin concentration was suppressed in sedated, critically ill patients, when compared to non-sedated controls and the frequency of delirium was elevated in sedated patients. Trail registration Clinicaltrials.gov (NCT01967680) on October 23, 2013 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Circadian | |
| 650 | 4 | |a Delirium | |
| 650 | 4 | |a Melatonin | |
| 650 | 4 | |a Non-sedation | |
| 650 | 4 | |a Rhythm | |
| 650 | 4 | |a Sedation | |
| 700 | 1 | |a Knudsen, Torben |e verfasserin |4 aut | |
| 700 | 1 | |a Strøm, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Lauridsen, Jørgen T |e verfasserin |4 aut | |
| 700 | 1 | |a Jennum, Poul J |e verfasserin |4 aut | |
| 700 | 1 | |a Toft, Palle |e verfasserin |4 aut | |
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