Is Delirium After Cardiac Surgery Related to Plasma Amino Acids and Physical Condition?

Abstract

The authors studied interrelationships between plasma levels of amino acids, physical condition (as apparent from cortisol, albumin, and thyroid hormone concentrations), and postoperative delirium in 296 patients undergoing elective cardiac surgery. Both plasma tryptophan (Trp) and ratio of Trp to the other large neutral amino acids (oLNAA) were reduced in delirious patients compared with control patients. The lower availability of Trp for the brain in delirious patients may lead to decreased serotonergic function. Besides, the ratio of phenylalanine (Phe) to the oLNAA was increased in delirium, which may result in a higher synthesis of cerebral dopamine and norepinephrine. Delirious patients were also in poorer physical condition than nondelirious patients, having decreased albumin level and increased ratio of inactive reverse triiodothyronine (T3) to active T3. Decreased Trp and increased Phe availability may give rise to an imbalance in cerebral neurotransmitters and thus contribute to delirium.

Septic encephalopathy: does inflammation drive the brain crazy?

“…90,91 Furthermore, elevated CNS serotonin activity is postulated to occur in hepatic encephalopathy, and serotonin syndrome secondary to the withdrawal of serotonin reuptake inhibitors resembles the clinical picture of SE. 92,93 Brain serotonin synthesis depends on the availability of tryptophan (Trp), and dopamine and norepinephrine production requires tyrosine (Tyr) and phenylalanine (Phe). 94 Despite the fact that most delirium theories suggest that an increase in amines drives delirium, in healthy volunteers the administration of LPS increases the cerebral delivery and influx of Phe.…”

Pathophysiology of Delirium in the Intensive Care Unit

“…To date, studies examining associations between surgery and delirium have investigated microemboli migration [149][150][151], hypoperfusion [64,137,[152][153][154], inflammatory responses [155][156][157], changes in hormone levels [158][159][160][161], and local and general anesthesia [64,133,162,163]. Gottesman and colleagues [152] hypothesized that a drop in the mean arterial pressure may put patients at risk for early cognitive dysfunction.…”

Commentary on "Large Neutral Amino Acid Changes and Delirium in Febrile Elderly Medical Patients": Do Amino Acids Play a Role in the Pathophysiology of Delirium?

“…In 296 patients undergoing elective cardiac surgery, a high plasma ratio of PHE/oLNAA was reported to be an independent preoperative predictor for postoperative delirium (6), in accordance with the suggestion of Flacker and Lipsitz that baseline differences in PHE/oLNAA ratios may predispose to delirium. Also, plasma levels of PHE and TRP increased for all patients during surgery, while plasma TRP and TRP/oLNAA ratios were significantly lower and PHE/oLNAA significantly higher in delirious patients compared to control patients (7).…”

“…Plasma elevation of PHE may thus be explained by decreased conversion into its metabolites in the liver, because PHE hydroxylase needs tetrahydrobiopterin as a cofactor. In the presence of illness, tetrahydrobiopterin may be reduced secondary to a low T 3 syndrome and decreased production of ATP (7).…”