Increased CSF levels of aromatic amino acids in hip fracture patients with delirium suggests higher monoaminergic activity

Leiv Otto Watne,Frede Frihagen,Durk Fekkes,Knut Engedal,Anette Hylen Ranhoff,Johan Raeder,Bjørnar Hassel,Torgeir Bruun Wyller,Farrukh Abbas Chaudhry,Ane-Victoria Idland

doi:10.1186/s12877-016-0324-0

Abstract

BackgroundTo examine whether delirium in hip fracture patients was associated with changes in the levels of amino acids and/or monoamine metabolites in cerebrospinal fluid (CSF) and serum.MethodsIn this prospective cohort study, 77 patients admitted with an acute hip fracture to Oslo University Hospital, Norway, were studied. The concentrations of amino acids in CSF and serum were determined by high performance liquid chromatography. The patients were assessed daily for delirium by the Confusion Assessment Method (pre-operatively and post-operative day 1–5 (all) or until discharge (delirious patients)). Pre-fracture dementia status was decided by an expert panel. Serum was collected pre-operatively and CSF immediately before spinal anesthesia.ResultsFifty-three (71 %) hip fracture patients developed delirium. In hip fracture patients without dementia (n = 39), those with delirium had significantly higher CSF levels of tryptophan (40 % higher), tyrosine (60 % higher), phenylalanine (59 % higher) and the monoamine metabolite 5-hydroxyindoleacetate (23 % higher) compared to those without delirium. The same amino acids were also higher in CSF in delirious patients with dementia (n = 38). The correlations between serum and CSF amino acid levels were poor.ConclusionHigher CSF levels of monoamine precursors in hip fracture patients with delirium suggest a higher monoaminergic activity in the central nervous system during delirium in this patient group.

Highlights

To examine whether delirium in hip fracture patients was associated with changes in the levels of amino acids and/or monoamine metabolites in cerebrospinal fluid (CSF) and serum
Patients with delirium were older, had more often dementia, had higher APACHE II and more activities of daily living (ADL) impairment compared to patients without delirium (Table 1)
In patients with pre-fracture dementia (n = 38) the same four amino acids were highest in delirious patients, statistically significant only for tyrosine, phenylalanine and methionine

Summary

Introduction

To examine whether delirium in hip fracture patients was associated with changes in the levels of amino acids and/or monoamine metabolites in cerebrospinal fluid (CSF) and serum. Aromatic amino acids are precursors for the monoamines dopamine, noradrenaline and serotonin, which have important roles in attention and cognition and have been of interest in delirium research [6]. Phenylalanine and tyrosine (dopamine and noradrenaline precursors) levels have been found to be elevated in serum in patients with delirium [8,9,10] Both increased and decreased serum levels of the serotonin precursor tryptophan have been reported in patients with delirium [10, 11]. Whether such changes in serum levels translate to the central nervous system is unclear

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