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 .