Shock – Classification and Pathophysiological Principles of Therapeutics

Abstract

The management of patients with shock is extremely challenging because of the myriad of possible clinical presentations in cardiogenic shock, septic shock and hypovolemic shock and the limitations of contemporary therapeutic options. The treatment of shock includes the administration of endogenous catecholamines (epinephrine, norepinephrine, and dopamine) as well as various vasopressor agents that have shown efficacy in the treatment of the various types of shock. In addition to the endogenous catecholamines, dobutamine, isoproterenol, phenylephrine, and milrinone have served as the mainstays of shock therapy for several decades. Recently, experimental studies have suggested that newer agents such as vasopressin, selepressin, calcium-sensitizing agents like levosimendan, cardiac-specific myosin activators like omecamtiv mecarbil (OM), istaroxime, and natriuretic peptides like nesiritide can enhance shock therapy, especially when shock presents a more complex clinical picture than normal. However, their ability to improve clinical outcomes remains to be proven. It is the purpose of this review to describe the mechanism of action, dosage requirements, advantages and disadvantages, and specific indications and contraindications for the use of each of these catecholamines and vasopressors, as well as to elucidate the most important clinical trials that serve as the basis of contemporary shock therapy.

Evidences for Inotropism Triggered by Simultaneous Antegrade And Retrograde Myocardial Perfusion in A Swine Model

“…The results observed in this experimentation confirmed inotropic properties triggered by simultaneous SMR and antegrade LAD perfusion supported by electrophysiological adaptations that showed a rapid increase in diastolic durations increasing cardiac filling with a moderate chronotropism similar to the effects produced by Levosimendan [28]. We cannot exclude that these adaptations are likely to depend on paracrine regulations triggered by changes in tissue oxygenation and patterns of perfusion.…”

Diastolic dysfunction and impaired cardiac output reserve in dysmetabolic nonhuman primate with proteinuria

“…Dobutamine is mainly a sympathetic activator with b1-adrenoreceptor (AR) activity on myocytes mediating inotropic effect, b2-AR activity on vascular smooth muscle cells causing vasorelaxation, thus reducing peripheral vascular resistance, and a1-AR activity mediating chronotropic effect [22][23][24]. It is used in the clinic for decompensated congestive heart failure.…”

Diastolic Dysfunction and Impaired Cardiac Output Reserve in Dysmetabolic Nonhuman Primate With Proteinuria

“…Therefore, similar to what was seen in the systolic parameters, the MetS NHPs with proteinuria had preserved global cardiac function under rest condition, but DSE unmasked the compromised cardiac output reserve. Dobutamine is mainly a sympathetic activator with b1-adrenoreceptor (AR) activity on myocytes mediating inotropic effect, b2-AR activity on vascular smooth muscle cells causing vasorelaxation, thus reducing peripheral vascular resistance, and a1-AR activity mediating chronotropic effect [22][23][24]. It is used in the clinic for decompensated congestive heart failure.…”