Septic shock inotropes

Septic shock Sepsis with hypotension, despite fluid resuscitation, along with the presence of perfusion abnormalities. Patients who are on inotropic or vasopressor agents may not be hypotensive at the time perfusion abnormalities are measured. Multiple-Organ Dysfunction Syndrome (MODS) Presence of altered organ function requiring intervention to maintain homeostasis. 

Vasopressin levels are increased during hypotension to maintain blood pressure by vasoconstriction. However, there is a vasopressin deficiency in septic shock. Low doses of vasopressin increase MAP, leading to the discontinuation of vasopressors. However, routine use of vasopressin is not recommended because of lack of evidence of efficacy. Vasopressin is a direct vasoconstrictor without inotropic or chronotropic effects and may result in decreased cardiac output and hepatosplanchnic flow. Vasopressin use may be considered in patients with refractory shock despite adequate fluid resuscitation and high-dose vasopressors.24,27-28... 

Dopamine is used in the treatment of shock owing to inadequate cardiac output (cardiogenic shock), which may be due to myocardial infarction or congestive heart failure. It is also used in the treatment of septic shock, since renal circulation is frequently compromised in this condition. An advantage of using dopamine in the treatment of shock is that its inotropic action increases cardiac output while dilating renal blood vessels and thereby increasing renal blood flow. 

Oj effects noradrenaline (with slight P effect on heart) is selectively released physiologically where it is wanted as therapeutic agents for hypotensive states (excepting septic shock) dopamine and dobutamine are preferred (for their cardiac inotropic effect). Also having predominantly effects are imidazolines (xylometazoline, oxymeta-... 

After adequate fluid resuscitation has been established, inotropic support is usually required. Noradrenaline is the inotrope of choice for septic shock its potent a-adrenergic effect increases the mean arterial pressure and its modest Pj effect may raise cardiac output, or at least maintain it as the peripheral vascular resistance increases. Dobutamine may be added further to augment cardiac output. 

Noradrenaline is used when vasoconstriction is the first priority, plus some slight cardiac inotropic effect, e.g. septic shock. 

Arger et al 1999) however, the coadministration of dopamine opposes this effect and increases renal blood flow (Schaer et al 1985). Coadministration of norepinephrine (noradrenaline) and dobuta-mine to foals with septic shock increased urine production and blood pressure (Corley et al 2000). Norepinephrine (noradrenaline) should be reserved for horses with sepsis and used in conjunction with inotropes and monitoring of urine output. The recommended i.v. dose rates are shown in Table 12.3. 

Derangements in adrenergic receptor sensitivity or activity frequently result in resistance to vasopressor and inotropic therapy in critically ill patients. These changes may be a function of endogenous catecholamine concentrations, dose/duration of exposure to and type of exogenously administered vasopressors, stage of septic shock, preexisting illness, and other factors. 

Therapy with vasopressors and inotropes is continued until the myocardial depression and vascular hyporesponsive-ness of septic shock improve, usually measured in hours to days. Discontinuation of vasopressor or inotropic therapy should be executed slowly therapy should be "weaned" to avoid a precipitous worsening in regional and systemic hemodynamics. 

TABLE 23—3. Receptor Pharmacology of Selected Inotropic and Vasopressor Agents Used in Septic Shock ... 

Vasopressin is emerging as a potentially useful therapy in the hemodynamic support of vasodilatory septic shock. Case series and small clinical trials have reported its use in patients who remain hypotensive on vasopressors. Arginine vasopressin has little pressor activity in normal subjects but markedly increases blood pressure when sympathetic nerve function is impaired, including in septic shock. Unlike the catecholamine vasopressors, vasopressin is a direct vasoconstrictor agent and does not have inotropic or chronotropic effects. As a result, it may decrease cardiac output and hepatosplanchnic flow. In fact, studies of vasopressin in septic shock generally do not enroll patients with a cardiac index of less than 2 to 2.5 L/m per minute. 

Levosimendan is a novel inotropic calcium-sensitizing drug. In advanced congestive heart failure, it improves cardiac contractility by sensitizing troponin C to calcium. It has been used recently in a porcine model of endotoxin-induced septic shock, in which pretreatment with levosimendan improved cardiac output and systemic and gut oxygen delivery." There are currently two ongoing clinical trials of levosimendan in septic shock. The role of levosimendan in the supportive management of circulatory failure in sepsis remains to be determined. 

FIGURE 23-3. Algorithmic approach to the use of vasopressors and inotropes in septic shock. Algorithmic approach is intended to be used in conjunction with clinical judgment, hemodynamic monitoring parameters, and therapy end points, as discussed in the text. (Modified from ref 3.)... 

Further pharmacotherapeutic and outcomes studies are still required to elucidate the place in therapy that individual vasopressors and inotropes or their combinations occupy in the supportive care of patients with bacteremia or septic shock. As supportive therapy, it is imperative that primary therapy aimed at the source of (antimicrobials) and consequences of (anticytokines) infection be initiated quickly to afford the patient the best chance of survival. Once this is accomplished, then we wfll need to direct our efforts to pharma-coeconomics and the cost-effectiveness of these therapies. 

Oldner A, Konrad D, Weitzberg E, et al. Effects of levosimendan, a novel inotropic calcium-sensitizing drug, in experimental septic shock. Crit Care Med 2001 29 2185-2193. 

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