Current drug targets
-
Current drug targets · Sep 2009
Reducing the risk of major elective non-cardiac surgery: is there a role for levosimendan in the preoperative optimization of cardiac function?
Patients with heart failure undergoing non-cardiac surgery still have an unacceptably high morbidity and mortality. Compromised myocardial physiologic reserves in combination with extensive surgery and anesthesia appear to play a crucial role in determining high perioperative morbidity and mortality. Nevertheless, several other mechanisms and pathways such as metabolic factors, ischemia-reperfusion conditions, neurohormonal activation, inflammation and oxidative stress contribute to the adverse outcome. ⋯ At the cellular level in the heart, kidney, lung, liver as well as the gut, levosimendan exerts protective preconditioning effects secondary to activation of adenosine triphosphate (ATP)-sensitive potassium channels. Taking into account these multiple but complementary mechanisms, levosimendan appears to be a suitable agent for preoperative optimization of cardiac functions in heart failure patients undergoing major elective surgery. Nevertheless, large-scale trials are needed before final conclusions can be drawn on the use of levosimendan in this indication.
-
Acute severe asthma is characterized by a state of airway inflammation and increased bronchiolar smooth-muscle tone that leads to increased resistance to expiration and lung hyperinflation. Despite the better knowledge of its pathophysiology, the incidence and severity of asthma in the last twenty years is increased worldwide, although with significant age and geographic variation. As a result, the number of patients requiring more intensive medical therapy has also increased. ⋯ The use of inhalational anesthetic agents for treatment of severe status asthmaticus has been documented in case reports, case series and small uncontrolled studies. Their use may be considered in any mechanically ventilated patients whose severe bronchospasm failed to respond to maximal medical treatment. In the present review article, we aim to provide a brief description of the physio-pathological and clinical features of acute severe asthma, and of the principles of treatment, focusing our attention on the use of the inhalational anesthetics in severe patients requiring mechanical ventilation and not responding to conventional therapy.
-
Current drug targets · Sep 2009
ReviewUse of corticosteroids in critically ill septic patients : a review of mechanisms of adrenal insufficiency in sepsis and treatment.
Adrenal insufficiency has being reported with increased frequency in critical ill patients with sepsis and other inflammatory states. Its incidence varies widely depending on the criteria used to define it and the patient population studied. Increased glucocorticoid action is essential in the stress response to acute injury and even minor degrees of adrenal insufficiency can be fatal. ⋯ Whether exogenous corticosteroid support may be beneficial in critical illness is still matter of debate: most international guidelines recommend that the decision to treat patients with corticosteroids should be based on clinical criteria (low blood pressure poorly responsive to vasopressor despite adequate fluid resuscitation) rather than on tests of the hypothalamic-pituitary-adrenal axis alone. As regards specifically the role of steroids in the treatment of sepsis and septic shock, at present there are no strong evidence-based recommendations. More studies are needed to reach consensus about several issues: which is the best target population, whether a cosyntropin test should be used to guide treatment, whether fludrocortisones should be given along with hydrocortisone, and how long treatment should continue.
-
Critical illness and particularly sepsis are associated with a significant redox imbalance resulting from an increased production of oxidant species and a decrease in endogenous antioxidant defences. In critical patients sources of oxidative stress include the mitochondrial respiratory electron transport chain, xanthine oxidase activation, the respiratory burst associated with neutrophil activation, and arachidonic acid metabolism. Several endogenous antioxidants have been identified including enzymes, like superoxide dismutases and glutathione peroxidase, vitamins and other molecules such as uric acid and bilirubin. ⋯ Melatonin is a promising molecule that deserves the attention of future research, as well as vitamin C. Further studied should also try to establish the more beneficial combination of antioxidants, as well as the doses, and the timing of administration. When such problems will be resolved hopefully results about antioxidant therapy in critical illness will be more univocal and promising.
-
It has been estimated that nosocomial fever occurs in approximately one-third of hospitalized patients. The incidence is even higher in critically-ill patients in whom both infectious and noninfectious etiologies of fever are common. ⋯ There is widespread acceptance that in most if not all critically ill neurologic patients fever should be treated but still it is not clear if fever per se in nonneurologic critically ill patients should be treated too. We review physical and pharmacological methods presently utilized to treat fever in critically ill patients.