Activation of adrenergic alpha-2 receptors causes hypotension, bradycardia, sedation, arterial and venous vasoconstriction, decreased presynaptic transmitter release, thrombus stabilization, hypothermia, decreased gastric acid secretion and motility, inhibition of lipolysis and insulin from pancreas [1]. Endogenous noradrenaline release increases due to increased sympathetic activity in septic shock. According to the hypothesis of Pichot et al., Blinding of sympathetic activity with an alpha-2 agonist in septic shock improves vascular reactivity by creating alpha-1 receptor upregulation and thereby decreases the need for vasopressors [2]. It has been found that the response to norepinephrine decreases with the application of lipopolysaccharide in rats, and administration of alpha-2 agonists increases this response [3].

In human whole blood cultured with lipopolysaccharide, dexmedetomidine suppresses the release of tumor necrosis alpha (TNF-α) interleukins 6 and 8 (IL-6, IL-8), high mobility group box 1 (HMGB-1), and this effect is reversed with yohimbine. respectively. It has been reported that dexmedetomidine is suppressed by alpha-2 adrenergic receptors on the production of proinflammatory mediators [4]. HMGB-1 is a proinflammatory mediator closely associated with mortality in septic patients. Dexmedetomidine has been found to inhibit the translocation of HMGB-1 from nucleus to cytoplasm and HMGB-1 mRNA expression in lipopolysaccharide-activated macrophages [5]. Dexmedetomidine has been found to decrease mortality and decrease serum IL-6 and TNF-α levels in the experimental sepsis model and decrease HMGB-1 mRNA in the lung [6]. Dexmedetomidine has been reported to reduce acute kidney damage due to lipopolysaccharide in septic rats. In this study, plasma creatinine, IL-6 and 8, TNFα and HMGB-1 levels were found to be significantly lower in the dexmedetomidine group [7]. Dexmedtoimide has been found to significantly reduce mortality and pulmonary inflammation in septic rats and inhibit toll like receptor / myeloid differatiation factor 88 (TLR-4 / MyD88) expression and nuclear factor kap B (NFkB) activation. Dexmedetomidine has been reported to reduce mortality and lung inflammation by suppressing the TLR-4 / MyD88 / NFkB pathway [8]. Dexmedetomidine reduces TNF-α and IL-6 levels in septic rats bronchoalveolar lavage fluid and plasma, and inhibits TLR-4 and MyD88 expression in mRNA and inhibits extracellular signal-regulated kinase 1/2 phosphorylation (ERK1 / 2) and NFkB activation in lung tissue. is shown [9].

Dexmedetoimidine has been shown to activate the cholinergic anti-inflammatory pathway linked to alpha7 nicotinic acetylcholine receptors [10,11]. The spleen plays an important role in the neural cholinergic anti-inflammatory pathway. Dexmedetoimide has been shown to decrease NFkB activation due to lipopolysaccharide in septic rats and reduce TNF-α and IL-6 production at the level of mRNA in the spleen [12]. Atakan et al. Examined the effects of dexmedetomidine on liver histopathology in the model of sepsis in rats [13]. They found that hepatic central venous congestion, congestion and dilatation in hepatic sinusoids, and inflammation in the portal area were significantly lower in the dexmedetomidine + sepsis group compared to the sepsis group. It has been reported that dexmedetomidine is an option to prevent liver dysfunction due to sepsis [14].

The effects of propofol and dexmedetomidine on inflammatory response and intraabdominal pressure in patients with severe sepsis after abdominal surgery were compared. TNF-α and IL-1 and 6 and intraabdominal pressure were found to be significantly lower at the 24^th and 48^th hours compared to the propofol group in the dexmedetomidine group [15]. The effects of dexmedetomidine on survival in septic patients were investigated by systematic review of 6 studies involving 242 patients. Dexmedetomidine has been found to reduce short-term mortality without affecting the length of stay in intensive care. They stated that the number of clinical studies is insufficient and further studies are required [16]. Clinical studies are needed to examine the effects of dexmedetomidine on survival, organ functions and vasopressor requirement in sepsis.