<ul><li>Is an unusually low blood pressure at which a patient is often symptomatic or manifests clinical features. </li></ul><ul><li>These may be </li></ul><ul><ul><li>Relatively mild and non-specific (e.g. dizziness or malaise) </li></ul></ul><ul><ul><li>Organ-specific (e.g. coma or chest pain) </li></ul></ul><ul><ul><li>Or associated with systemic features of shock </li></ul></ul>
<ul><li>Definition </li></ul><ul><li>Is currently best defined as a multifactorial syndrome resulting in inadequate tissue perfusion and cellular oxygenation </li></ul><ul><li>Regardless of cause or severity, all forms of shock have the commonality of perfusion inadequate to meet metabolic demands at the cellular level </li></ul><ul><li>Decreased organ perfusion leads to tissue hypoxia, anaerobic metabolism, activation of an inflammatory cascade, and eventual organ dysfunction </li></ul>
<ul><li>An endogenous catecholamine that functions as a central neurotransmitter and a synthetic precursor of norepinephrine and epinephrine </li></ul><ul><li>When administered intravenously, the effects of dopamine are mediated by dose-dependent stimulation of dopaminergic and adrenergic receptors, and by stimulation of norepinephrine release from nerve terminals </li></ul><ul><li>At low doses (less than 5 µg per kg per minute), dopamine predominantly stimulates dopaminergic receptors in renal, mesenteric, and coronary vessels with minimal adrenergic effects so-called renal-dose dopamine augments renal blood flow, glomerular filtration rate, and natriuresis, with little effect on blood pressure </li></ul>
<ul><li>Moderate doses of dopamine (5 to 10 µg per kg per minute) stimulate β 1-adrenergic receptors in the myocardium, augmenting cardiac output by increasing contractility and, to a lesser extent, heart rate </li></ul><ul><li>At higher doses (greater than 10µg per kg per minute), α 1-adrenegic receptor stimulation predominates, resulting in systemic arteriolar vasoconstriction. The overall effects of dopamine at the highest doses resemble those of norepinephrine </li></ul>
Van de Borne P, Oren R, Somers VK: Dopamine depresses minute ventilation in patients with heart failure. Circulation 98:126-131, 1998.
<ul><li>When dopamine is used in patients with acute decompensated heart failure, increased venous tone and pulmonary arterial pressure may exacerbate pulmonary edema in the setting of already high cardiac filling pressures </li></ul><ul><li>There is mounting evidence that dopamine adversely affects splanchnic perfusion at doses usually required to treat septic shock </li></ul><ul><li>Studies showed that in patients with septic shock randomly assigned to treatment with norepinephrine or dopamine, gastric intramucosal pH worsened significantly in patients treated with dopamine despite similar improvements in mean arterial pressure  . Thus, the use of dopamine in septic shock may be associated with splanchnic shunting, impairment of gastric mucosal oxygenation, and increased risk of gastrointestinal bleeding  </li></ul>Adverse effects 1. Marik PE, Mohedin M: The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in hyperdynamic sepsis. JAMA 272:1354-1357, 1994. 2. Schleien CL, Osmond MH, Hickey R, et al: Postresuscitation management. Ann Emerg Med 37:S182-195, 2001.
<ul><li>An endogenous catecholamine that is a potent nonselective agonist of α and β -adrenergic receptors </li></ul><ul><li>Stimulation of myocardial β 1 and β 2 receptors increases contractility and heart rate, resulting in a rise in cardiac output </li></ul><ul><li>Cardiac output is further augmented by an increase in venous return as a result of α 1-mediated venoconstriction </li></ul><ul><li>Blood flow to skeletal muscles is increased owing to β 2-mediated vasodilation </li></ul><ul><li>With very low-dose infusions of epinephrine (0.01 to 0.05 µg per kg per minute), β adrenergic mediated positive chronotropic and inotropic effects predominate </li></ul><ul><li>Diastolic blood pressure and overall peripheral vascular resistance may actually decrease owing to vasodilation in skeletal muscle </li></ul><ul><li>With higher doses of epinephrine, stimulation of α -adrenergic receptors in precapillary resistance vessels of the skin, mucosa, and kidneys outweighs β 2-mediated vasodilation in skeletal muscle, causing increased mean and systolic blood pressure </li></ul>
<ul><li>Epinephrine plays a central role in cardiovascular resuscitation </li></ul><ul><li>Epinephrine is also used to reverse hypotension with or without bradycardia after cardiopulmonary bypass or cardiac transplantation  </li></ul><ul><li>Because of its adverse effects on splanchnic and renal blood flow and potential for inducing myocardial ischemia and tachyarrhythmias, epinephrine has generally been regarded as a second-line agent in the management of septic shock </li></ul><ul><li>Epinephrine should be avoided in patients taking β -adrenergic antagonists, as unopposed α -adrenergic vasoconstriction may cause severe hypertension and cerebral hemorrhage </li></ul><ul><li>1 . McKinlay KH, Schinderle DB, Swaminathan M, et al: Predictors of inotrope use during separation from cardiopulmonary bypass. J Cardiothorac Vasc Anesth 18:404-408, 2004. </li></ul>
<ul><li>An endogenous catecholamine that is a potent β 1- and α 1-adrenergic agonist, with little β 2-activity </li></ul><ul><li>The main cardiovascular effect of norepinephrine is dose-dependent arterial and venous vasoconstriction owing to α -adrenergic stimulation </li></ul><ul><li>The positive inotropic and chronotropic effects of β 1-stimulation are generally counterbalanced by the increased afterload and reflex vagal activity induced by the elevated systemic vascular resistance. Thus, heart rate and cardiac output usually do not change significantly, although cardiac output may increase or decrease depending on vascular resistance, left ventricular function, and reflex responses </li></ul>
<ul><li>Norepinephrine, when infused at doses ranging from 0.5 to 30.0 µg per minute, is a potent vasopressor </li></ul><ul><li>Although generally reserved as a second-line agent or used in addition to other vasopressors in cases of severe distributive shock, norepinephrine is emerging as an agent of choice for the management of hypotension in hyperdynamic septic shock </li></ul>
<ul><li>In a small, prospective double-blind trial, Martin et al.  randomized patients with hyperdynamic septic shock to dopamine or norepinephrine titrated to a mean arterial pressure greater than or equal to 80 mm Hg or systemic vascular resistance greater than 1,100 dynes per second per cm -5 , or both. Although only 5 of 16 patients randomized to dopamine were able to achieve these endpoints, 15 of 16 patients randomized to norepinephrine were successfully treated with a mean dose of 1.5 µg per kg per minute </li></ul><ul><li>Moreover, 10 of the 11 patients who remained hypotensive on high-dose dopamine improved with the addition of norepinephrine </li></ul><ul><li>A subsequent prospective, nonrandomized, observational study suggested that in adults with septic shock treated initially with high-dose dopamine or norepinephrine, the use of norepinephrine was associated with improved survival  </li></ul><ul><li>In the setting of sepsis, norepinephrine improves renal blood flow and urine output  , although large doses may be required to achieve these effects due to α -receptor down-regulation  </li></ul>1. Martin C, Papazian L, Perrin G, et al: Norepinephrine or dopamine for the treatment of hyperdynamic septic shock? Chest 103:1826-1831, 1993. 2. Martin C, Viviand X, Leone M, et al: Effect of norepinephrine on the outcome of septic shock. Crit Care Med 28:2758-2765, 2000. 3. Hollenberg SM, Ahrens TS, Annane D, et al: Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update. Crit Care Med 32:1928-1948, 2004. 4. Bellomo R, Giantomasso DD: Noradrenaline and the kidney: friends or foes? Crit Care 5:294-298, 2001.
<ul><li>A synthetic sympathomimetic amine that was derived from isoproterenol in an attempt to create a less arrhythmogenic positive inotrope with minimal vascular effects , potent nonselective β -and mild α -adrenergic stimulation  </li></ul><ul><li>Systemic vascular resistance is modestly reduced or may remain unchanged, as α 1-mediated vasoconstriction is counterbalanced by β 2-mediated vasodilation and reflex withdrawal of sympathetic tone that typically occurs in response to increased cardiac output </li></ul><ul><li>Dobutamine, by itself or in combination with other vasoactive drugs, is useful in the temporary support of myocardial function in patients with hypotension and poor end-organ perfusion, including those with acute decompensated heart failure as well as patients with concomitant septic shock and depressed cardiac function </li></ul><ul><li>1.Ruffolo RR Jr: The pharmacology of dobutamine. Am J Med Sci 294:244-248, 1987 </li></ul>
<ul><li>Dobutamine is generally initiated at an infusion rate of 2 µg per kg per minute and can be titrated up to 15 µg per kg per minute or higher to achieve the desired hemodynamic or clinical effects, or both </li></ul>1. Takkenberg JJ, Czer LS, Fishbein MC, et al: Eosinophilic myocarditis in patients awaiting heart transplantation. Crit Care Med 32:714-721, 2004.
<ul><li>N.B </li></ul><ul><li>Although systolic and mean arterial blood pressures typically increase, hypotension may occur if dobutamine is administered to a volume-depleted patient </li></ul><ul><li>Some patients with advanced heart failure may be resistant to dobutamine owing to β -receptor hyporesponsiveness or may develop tolerance after several days of a continuous infusion </li></ul>
<ul><li>Arginine vasopressin, an antidiuretic hormone, has recently emerged as a potential alternative to adrenergic vasopressors for the treatment of refractory vasodilatory shock </li></ul><ul><li>Although it has minimal pressor activity in normal subjects, vasopressin has been shown to improve blood pressure in patients with sepsis  and in patients with vasodilatory shock after cardiopulmonary bypass </li></ul><ul><li>Vasopressin may also be effective in the treatment of cardiac arrest unresponsive to epinephrine and defibrillation </li></ul>1. Landry DW, Levin HR, Gallant EM, et al: Vasopressin pressor hypersensitivity in vasodilatory septic shock. Crit Care Med 25:1279-1282, 1997.
Revised guidelines for advanced cardiovascular life support recommend vasopressin as an alternative to epinephrine for the treatment of adult shock-refractory ventricular fibrillation, as well as an adjunctive agent in the treatment of patients with vasodilatory shock, such as septic shock or sepsis syndrome, refractory to standard therapy
<ul><li>There are no large, randomized, well-controlled studies to guide the pharmacologic management of hypotension </li></ul><ul><li>The use of vasopressors and positive inotropes is generally based on data from animal studies and small, often poorly controlled clinical trials </li></ul><ul><li>The selection of the appropriate vasoactive agent should be made on a case-by-case basis , with attention to the known or suspected underlying cause of hypotension </li></ul>
<ul><li>It may be necessary to initiate a vasopressor as a temporizing measure even before the adequacy of intravascular volume repletion can be ensured </li></ul><ul><li>Dopamine in moderate to high doses may be a reasonable first choice given its combined positive inotropic and vasopressor effects </li></ul><ul><li>For severe hypotension (systolic blood pressure less than 70 mm Hg), a more potent α 1-adrenergic agonist such as norepinephrine should be considered </li></ul>
<ul><li>Dobutamine is the inotropic agent of choice </li></ul><ul><li>With frank cardiogenic shock or concomitant vasodilation, however, a drug with pressor action is usually needed. In this setting, dopamine can be used by itself or in combination with dobutamine </li></ul><ul><li>Patients with septic shock and related myocardial dysfunction, dobutamine can be added to norepinephrine or dopamine for added inotropic support </li></ul>
<ul><li>The most common clinical situation encountered in the intensive care setting is the hypotensive patient with peripheral vasodilation and low systemic vascular resistance due to sepsis </li></ul><ul><li>The ideal vasopressor agent in this setting remains controversial: Dopamine and norepinephrine are the two most commonly used drugs, with the latter often reserved for more severe or refractory cases of septic shock </li></ul><ul><li>Given the superior potency of norepinephrine and recent data demonstrating worsening splanchnic perfusion with high-dose dopamine, norepinephrine is emerging as the agent of choice for vasodilatory shock in sepsis </li></ul><ul><li>Dopamine may be used as an alternate agent or in cases in which positive inotropic effects are desirable </li></ul>
<ul><li>Current experience with phenylephrine is insufficient to assess its efficacy relative to older agents, although its peripheral selectivity and lack of positive chronotropic effects make it a theoretically useful agent in cases in which tachycardia, tachyarrhythmias, or both limit the use of other drugs </li></ul><ul><li>Epinephrine is the least selective of the catecholamines and is occasionally added for refractory septic shock </li></ul><ul><li>Vasopressin is emerging as an alternative to adrenergic agents, but its use for hypotension may be limited to patients with hemodynamic collapse that is resistant to traditional sympathomimetic amines </li></ul><ul><li>For patients refractory to multiple pressors, a trial of methylene blue should be considered [1,2] </li></ul>1-Kirov MY, Evgenov OV, Evgenov NV, et al: Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study. Crit Care Med 29:1860-1867, 2001. 2. Levin RL, Degrange MA, Bruno GF, et al: Methylene blue reduces mortality and morbidity in vasoplegic patients after cardiac surgery. Ann Thorac Surg 77:496-499, 2004
<ul><li>In the volume-resuscitated patient with persistent hypotension, vasoactive medications are administered with the goal of improving arterial pressure while avoiding myocardial ischemia, arrhythmias, and excess vasoconstriction </li></ul><ul><li>Although a mean arterial blood pressure of greater than 60 mm Hg is usually adequate to maintain autoregulatory blood flow to vital organs , some patients may require considerably higher pressures </li></ul><ul><li>Therefore, it is essential to use other indicators of global and regional perfusion in addition to the mean arterial pressure to guide therapy. Altered mental status, oliguria, and cool skin are important clinical signs of poor perfusion, but are somewhat nonspecific. The clinical use of mixed venous oxygen saturation and serum lactate level, as well as intramucosal pH monitoring by gastric tonometry remains unproven </li></ul>
<ul><li>Although some clinicians have advocated achieving (supranormal) levels of oxygen delivery in the treatment of critically ill patients, this approach is controversial </li></ul><ul><li>A recent metaanalysis in critically ill patients found that various approaches to hemodynamic optimization reduced mortality when patients were treated early to achieve hemodynamic goals before the development of organ failure and when therapy produced differences in oxygen delivery </li></ul><ul><li>Moreover, the administration of vasopressors to intravascularly depleted patients can worsen end-organ perfusion </li></ul><ul><li>In patients who do not respond adequately to initial fluid boluses and brief infusion of vasopressors, invasive hemodynamic monitoring may aid in optimizing filling pressures and selecting the appropriate vasoactive agent </li></ul>Clinical Use of Vasoactive Drugs
<ul><li>Intraarterial cannulation and direct monitoring of blood pressure is suggested during prolonged vasopressor use </li></ul><ul><li>Drugs should be administered through central venous catheters via volumetric infusion pumps that deliver precise flow rates </li></ul><ul><li>Abrupt lowering or discontinuation of vasoactive drugs should be avoided to prevent rebound hypotension </li></ul><ul><li>Furthermore, an individual patient's response to an agent may diminish with time owing to several mechanisms, including adrenergic receptor desensitization </li></ul>Clinical Use of Vasoactive Drugs
<ul><li>The administration of less-selective drugs (e.g., norepinephrine) to a patient receiving chronic beta-blockade can result in unopposed α - adrenergic stimulation. Another well-described interaction is the exaggerated response to some catecholamines in individuals taking monoamine oxidase inhibitors. The starting dose for these patients should be less than 10% of the usual dose </li></ul>Clinical Use of Vasoactive Drugs