Table 1.

Studies regarding pathomechanisms of delirium—design and main characteristics.

Pathomechanisms	Authors and Reference Number	Study Design	Number of Patients	Results
Hypoxia	Funk et al. [16]	Prospective controlled clinical study	15 septic shock patients	Decrease in cerebral saturation corresponds to the incidence of delirium
	Mikkelsen et al. [17]	Prospective, multicentre cohort clinical study	406 adult patients treated for ARDS	Low PaO2 was associated with cognitive impairment
	Hopkins et al. [18]	Prospective controlled clinical study	120 adult patients treated for ARDS	Hypoxia assessed as SaO2 < 90% is associated with long-term neurocognitive disorders
Hyperoxia	Kupiec et al. [19]	Retrospective clinical study	93 cardiac surgery patients	Hyperoxia defined as PaO2 > 120 mmHg is associated with the occurrence of postoperative delirium
	Mutch et al. [20]	Prospective clinical study	12 healthy volunteers	Disturbance in cerebral blood flow following hyperoxia corresponds with postoperative neuropsychological disorders
	Lopez et al. [24]	Prospective controlled clinical study	310 cardiac surgery patients	Hyperoxia defined as any intraoperative cerebral oxygenation greater than baseline
Neuroinflammation	Velagapudi et al. [36]	Experimental, behavioural and histological study	61 animals undergoing orthopaedic surgery	Orthopaedic surgery leads to microglial activation, astrogliosis and brain blood-barrier disruption
Disorders in neurotransmitters	Adam et al. [47]	Prospective observational study	114 cardiac surgery patients	Decrease in acetylcholine hydrolysing enzyme activity increases risk for delirium
	John et al. [48]	Prospective observational study	251 cardiac surgery patients	There are no correlations between acetylcholine hydrolysing enzyme activity and risk of delirium
	Yilmaz et al. [54]	Prospective observational study	137 cardiac surgery patients	Dopamine infusion is an independent risk factor for delirium
	Yoshitaka et al. [57]	Prospective observational study	40 critically ill patients	Plasma GABA activity is associated with delirium
	Wyrobek et al. [61]	Prospective observational study	77 elderly patients undergoing spinal surgery	Decrease in the brain-derived neurotrophic factor is associated with delirium
	Madsen et al. [67]	Prospective observational study	30 healthy volunteers	Disorders in 5-HT4 receptor correlate with impaired memory and risk for neuropsychiatric disorders
Tryptophan metabolism and kynurenine pathway dysregulation	Kozak et al. [75]	Experimental, behavioural and histological study	Animal study	Elevated brain kynurenic acid impairs cognitive function
	Valle et al. [77]	Prospective observational study	62 HIV-infected patients	Elevated quinolinic acid is a risk factor for neurocognitive disorders
	Gulaj et al. [78]	Prospective observational study	34 patients with Alzheimer dementia	Plasma kynurenic acid and quinolinic acid correlate with impaired cognitive function
	Solvang et al. [79]	Prospective observational study	155 patients with dementia	Kynurenine had a nonlinear quadratic relationship with cognitive disorders
Gut microbiota dysregulation	Zhang et al. [93]	Experimental, behavioural study	11 pigs	Gut microbiota disorders induce delirium
	Liufu et al. [94]	Experimental, behavioural study	10 mice	Gut microbiota disorders induce delirium
	Liskiewicz et al. [96]	Prospective observational study	16 patients with major depression	Disorders in gut microbiota are associated with the severity of depression
	Huang et al. [97]	Prospective observational study	54 patients with major depression	Defects of the Firmicutes (gut bacteria) increase a risk for depression

Legend: ARDS—adult respiratory distress syndrome; GABA—gamma-amino butyric acid; HIV—human immunodeficiency virus; 5-HT4—5-hydroxytryptamine; PaO₂—partial pressure of oxygen; SaO₂—oxygen saturation.