Assessment of melatonin, cortisol and rest–activity rhythms in critically ill patients weaning from mechanical ventilation

Introduction

Acute illness adversely affects a patient's circadian rhythms. Minimising the delayed restoration of these rhythms may have patient benefits. The aims of this study were to investigate the acute effects of exogenous melatonin on the rest–activity rhythms of patients recovering from critical illness, and furthermore to analyse the rhythms and relationship between plasma melatonin and cortisol levels.

Methods

A randomised controlled trial in 24 critically ill patients weaning from mechanical ventilation. Ethics committee approval was granted and all patients provided written consent. Twelve patients in each group received placebo or 10 mg exogenous melatonin at 21:00 hours for four nights. Twelve plasma samples were taken periodically from the first 18 of these patients over a 24-hour period. Actigraphy was used to monitor patient activity. Rhythm analysis of plasma levels and activity data used single cosinor analysis and nonparametric parameters, respectively.

Results

Both groups were well matched. There were no significant differences between the groups in any of the rest–activity measures, which were abnormal and comparable with those previously reported [1]. There was a weak inverse correlation between plasma melatonin and cortisol levels (r = -0.22, P = 0.015). Seven of 18 patients had a circadian rhythm of plasma cortisol levels, while only two patients had a normal acrophase. Four of the nine placebo patients had a circadian rhythm of melatonin, but only one of these had a normal amplitude and acrophase. The plasma melatonin 24-hour area under the curve was significantly reduced compared with healthy elderly people (128.4 (112.6; 217.0) versus 464.5 (372.5; 594.0), P < 0.001). A moderate inverse relationship existed between the percentage plasma cortisol rhythm and patient intradaily variability (r = -0.70, P < 0.002).

Conclusion

Acute administration of exogenous melatonin did not result in significant differences in rest–activity rhythms between the groups. Most patients lacked circadian rhythms of plasma melatonin and cortisol levels, which were no longer phase locked. The amplitude of plasma melatonin levels are significantly suppressed.