Table 1 Relevant clinical and pre-clinical investigations supporting autonomic dysfunction in response to sepsis and septic shock (or endotoxic shock)
Markers | Main results | Type of studies | References |
|---|---|---|---|
Catecholamines/ neuroendocrine mediators | Endogenous catecholamine increase after a sympathetic insult (e.g., head-up tilt) was larger in sepsis survivors than in non-survivors. Mortality and morbidity were higher in patients with higher and more prolonged catecholamine burden | Clinical studies | Benedict and Rose [44], Ostrowski et al. [28], Boldt et al. [27], Schmittinger et al. [29] |
In the late phase of sepsis, animals showed reduced vasopressin release. Animal models of sinoartic denervation and bilateral carotid neurotomy showed an increase in catecholamines and TNF-alpha release | Animal studies | ||
Adrenergic receptors | Endotoxemia caused systemic α1-receptor downregulation in all organs investigated; tissue concentrations of interleukin-1β and TNF-α were markedly increased | Animal study | Bucher et al. [47] |
Patients presenting with sepsis or septic shock had extended deficits in β-adrenergic post-receptor signal transduction | Clinical study | Bernardin et al. [48] | |
HRV, BPV, BRS and chemoreflex sensitivity | BRS, chemoreflex sensitivity, and almost all HRV indexes were attenuated in MOF patients. Patients in whom organ function (SOFA score) increased significantly showed an increase in mean BP value and LF power in BP time series | Clinical studies | |
Reduced HRV indexes preceded sepsis-induced macro-hemodynamic alterations. HRV reduction was associated with pronounced parasympathetic inhibition and a sympatho-vagal balance shift. BRS was reduced after fecal peritonitis; overall variability, LF power, LF/HF ratio of HR, and LF power of MAP were all reduced. Denervated rats had the lowest BRS and survived the shortest time after the peritonitis. Endotoxic shock induced a very rapid impairment in baroreflex function, independent of the BP level. Septic shock induced an inversion of the physiological pulse pressure amplification; aortic time constant tau, aortic compliance and TPR were decreased; BRS and aortic time constant tau alterations were correlated | Animal studies | Pancoto et al. [8], Jarkovska et al. [78], Shi et al. [9], Shen et al. [56], Nardocci et al. [57] Radaelli et al. [5], Carrara et al. [82] | |
Autonomic centers | Septic shock is associated with neuronal and glial apoptosis within the autonomic centers, which is strongly associated with endothelial iNOS expression | Post mortem patient study | Sharshar et al. [55] |