Postoperative delirium: the tryptophan dyregulation model

Area of Science:

• Neuroscience
• Endocrinology
• Sleep Medicine

Background:

• Previous models linked postoperative delirium to elevated melatonin and central serotonin deficiency, explaining only hypoactive delirium.
• Recent findings associate reduced melatonin metabolites with hyperactive delirium and increased metabolites with hypoactive delirium, necessitating a revised model.

Purpose of the Study:

• To propose a modified hypothesis for postoperative delirium mechanisms.
• To explain both hyperactive and hypoactive delirium subtypes.
• To investigate the role of central tryptophan homeostasis.

Main Methods:

• Review and synthesis of existing literature on melatonin, serotonin, and delirium.
• Formulation of a new hypothesis based on updated findings regarding melatonin metabolites.
• Postulation of tryptophan homeostasis as a central factor.

Main Results:

• The initial melatonin-serotonin shortage model inadequately explains delirium subtypes.
• Disruptions in central tryptophan homeostasis are proposed to underlie both hyperactive (agitation) and hypoactive (somnolence) delirium.
• Altered urinary melatonin metabolite levels correlate with specific delirium subtypes.

Conclusions:

• Central tryptophan homeostasis disturbance is a unifying mechanism for postoperative delirium subtypes.
• Melatonin administration is hypothesized to restore tryptophan levels.
• Melatonin intervention may serve as a preventative strategy for postoperative delirium.