Septic shock vasopressors

Hydrocortisone 50 mg IV q6h or 100 mg IV q8h for 7 d in patients with septic shock requiring vasopressor support if relative adrenal insufficiency present... 

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. 

Hydrocortisone for septic shock patients refractory to resuscitation and vasopressors, with adrenal insufficiency. 

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... 

Stress-induced adrenal insufficiency complicates 9% to 24% of septic patients and is associated with increased mortality. Adrenal-insuffident patients are identified by a adrenocorticotropic hormone (ACTH) stimulation test. Patients are given 250 meg ACTH and a cortisol level is checked within 30 to 60 minutes. Responders are defined as a greater than 9-mcg/dL increase in cortisol and non-responders as a less than 9-mcg/dL increase in cortisol. Septic shock patients refractory to resuscitation and vasopressors, and with adrenal insufifidency (non-responders to the ACTH test) should be administered intravenous hydrocortisone 200 to 300 mg per day in three divided doses for 7 days.24,44... 

Vasopressin causes vasoconstrictive effects that, unlike adrenergic receptor agonists, are preserved during hypoxia and severe acidosis. It also causes vasodilation in the pulmonary, coronary, and selected renal vascular beds that may reduce pulmonary artery pressure and preserve cardiac and renal function. However, based on available evidence, vasopressin is not recommended as a replacement for norepinephrine or dopamine in patients with septic shock but may be considered in patients who are refractory to catecholamine vasopressors despite adequate fluid resuscitation. If used, the dose should not exceed 0.01 to 0.04 units/min. 

Corticosteroids were shown in a metaanalysis to improve hemodynamics and survival and reduce the duration of vasopressor support in septic shock. 

Corticosteroids can be initiated in septic shock when adrenal insufficiency is present or when weaning of vasopressor therapy proves futile. A daily dose equivalent to 200 to 300 mg hydrocortisone should be continued for 7 days. Adverse events are few because of the short duration of therapy. 

Further data have come from a review of the use of high doses of vasopressin (mean dose 0.47 U/minute) to replace noradrenaline (24). There were reductions in heart rate, cardiac index, and oxygen delivery. The authors recommended that the dose of vasopressin should not exceed 0.04 U/minute and that vasopressin should not be used as a single vasopressor agent in septic shock. 

Hemodjmamic and cardiac complications are the major limitations of high-dose aldesleukin and have been described in both adults (19,20) and children (21). Significant hypotension requiring meticulous maintenance therapy with intravenous fluids or low-dose vasopressors was observed in most patients (22). The clinical findings were very similar to the hemodynamic pattern seen in early septic shock. Aldesleukin-induced increases in plasma nitrate and nitrite concentrations correlated with the severity of hypotension (23). 

However, accumulating evidence supports the use of norepinephrine in patients with septic shock with a retrospective study demonstrating reduced mortality with norepinephrine over other vasopressors [106]. Furthermore, animal data demonstrates that reversal of septic hypotension with norepinephrine leads to increases in renal blood flow [107]. There are no studies that compare the renal outcomes between catecholamine therapy and vasopressin. 

Godlewski G, Malinowska B, Schlicker E (2004) Presynaptic cannabinoid CBl receptors are involved in the inhibition of the neurogenic vasopressor response during septic shock in pithed rats. Br J Pharmacol 142 701-708... 

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 ... 

Dopamine is frequently the initial vasopressor used in septic shock. Doses of 5 to 10 mcg/kg per minute are initiated to improve MAP. Most studies in patients with septic shock have shown that at these doses dopamine increases Cl by improving contractility and heart rate, resulting primarily from its effects. It increases arterial pressure and SVR as a result of both the increased cardiac output and, at higher doses (>10 mcg/kg per minute), as a result of the i effects. 

The clinical utility of dopamine as a vasopressor in the setting of septic shock is limited because large doses frequently are necessary to maintain cardiac output and blood pressure. At doses exceeding 20 mcg/kg per minute, there is limited further improvement in cardiac performance and regional hemodynamics. Its clinical use frequently is hampered by tachycardia and tachydysrhythmias, which may lead to myocardial ischemia. Although tachydysrhythmias theoretically should not be expected to occur until 5 to 10 mcg/kg per minute of dopamine, these fii effects are observed with doses as low as 3 mcg/kg per minute. They seem to be more prevalent in patients... 

Furthermore, tolerance to the vasodilatory effects of dopamine after 24 to 48 hours is evident in nonohguric patients with sepsis syndrome and has been reported in others. The lack of response to dopamine in septic shock patients on vasopressors and the tolerance that develops in responders to low-dose dopamine may be explained in part by time- and disease-dependent desensitization of the dopamine receptors this may not occur in those with sepsis syndrome or normal volunteers. Furthermore, differences in the extent of preexisting vasodilation and the pathophysiology of renal dysfunction in oliguric and septic shock patients also may contribute to the inconsistent responses seen to the administration of low doses of dopamine. 

Taken together, these recent data suggest that norepinephrine potentially should be repositioned as the vasopressor of choice in patients in septic shock because of its multiple benefits (1) It may decrease mortality in septic shock, (2) it attenuates inappropriate vasodilation and low global oxygen extraction, (3) it attenuates myocardial depression at unchanged or increased cardiac output and increased coronary blood flow, (4) it improves renal perfusion pressure and renal fi Itration, (5) it improves splanchnic perfusion, and (6) it is less hkely than other vasopressors to cause tachycardias and tachydysrhythmias. ... 

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