Effects of Dexmedetomidine Versus Ketamine on Inflammatory Response and Hemodynamic in Patients With Intraabdominal Sepsis: A Randomized Controlled Study

Severe sepsis is a major healthcare problem with a reported incidence of 1-2% in all hospitalizations. It is a major cause of death in intensive care units worldwide and is the second leading cause of death in noncoronary intensive care unit patients. Mortality remains high at 30-50% despite a better understanding of sepsis pathophysiology and improved advanced care in the past decade . It is defined as a life-threatening organ dysfunction with a Sequential Organ Failure Assessment (SOFA) score > 2 and a mortality of over 10% in hospitals . These patients suffer from circulatory disorders including decreased intravascular volume, peripheral vasodilatation, and myocardial dysfunction, increased metabolism, which may result in hypoxia due to the imbalance between systemic oxygen delivery and oxygen demand .

The pathophysiology of septic shock is well known. However, septic shock therapy is still limited, and the mortality of patients with septic shock remains high. The innate immune system is the first line of defense mechanism against pathogens . The activation of the immunocompetent cells, including macrophages, monocytes, natural killer cells, dendritic cells, and endothelial cells mediate the innate immune response to respond to pathogens or their components . Activated immune cells also secrete pro-inflammatory mediators such as cytokines interleukin (IL-1, IL-6, IL-8), tumor necrosis factor-α (TNF-α), prostaglandins, and histamine . These mediators act on vascular endothelial cells and cause vasodilation, increased vascular permeability, and recruitment of neutrophils to the tissue .

The coagulation cascade is activated locally by upregulating endothelial tissue factors and decreased thrombomodulin and its antithrombotic products .

Ketamine is one of the most rational anaesthetic and sedative agents for patients with sepsis because of its ability to maintain hemodynamics Ketamine also suppresses pro-inflammatory cytokines, apoptosis, and increases intracellular calcium . In the hyperinflammatory phase, ketamine can also reduce anti-inflammatory cytokines such as IL-10 in the hypoinflammatory phase. Ketamine was thought to reduce the risk of secondary infection in the hypoinflammatory phase. However, there has yet to be further research on this hypothesis . Therefore, ketamine is expected to be developed as a candidate for immunotherapy in sepsis.

Dexmedetomidine (alpha2 receptor agonist) has anti-inflammatory and anti-bacterial effects, which are superior to those of gamma-aminobutyric acid agonists, such as benzodiazepines and propofol . Furthermore, it also reduces neuronal apoptosis high doses of central alpha-2-agonists like dexmedetomidine increase vasopressor responsiveness Moreover, even in non-septic patients, alpha-2-agonists are associated with lower vasopressor requirements, increased arterial blood pressure, and enhanced baroreceptor response .