Septic shock norepinephrine

Small studies have shown improvement in glomerular filtration rate and gastrointestinal mucosal perfusion when norepinephrine is utilized in resuscitated septic shock... 

Not yet a first-line agent (the recent Vasopressin in Septic Shock Trial [VASST] showed no difference in 28-d mortality when vasopressin was compared with norepinephrine)... 

Norepinephrine is a potent a-adrenergic agent with less pronounced P-adrenergic activity. Doses of 0.01 to 3 mcg/kg per minute can reliably increase blood pressure with small changes in heart rate or cardiac index. Norepinephrine is a more potent agent than dopamine in refractory septic shock.24,27-28... 

Vasopressin is a peptide hormone produced by the hypothalamus and secreted by the posterior pituitary in response to stimulation. Normal stimuli for vasopressin release are hyperosmolarity and hypovolemia, with thresholds for secretion of greater than 280 mOsm/kg and greater than 20% plasma volume depletion. A number of other stimuli, such as pain, nausea, epinephrine, and numerous drugs, induce release of vasopressin. Vasopressin release is inhibited by volume expansion, ethanol, and norepinephrine. The physiological effect of vasopressin is to promote free water clearence by altering the permeability of the renal collecting duct to water. In addition, it has a direct vasoconstrictor effect. Consequently, vasopressin results in water retention and volume restoration. In patients with septic shock, vasopressin is appropriately secreted in response to hypovolemia and to elevated serum osmolarity (R14). 

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. 

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. 

Martin C, Viviand X, Leone M, and Thirion X. 2000. Effect of norepinephrine on the outcome of septic shock. Crit Care Med 28 2758-2765. 

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. 

Dopamine often is recommended as the initial catecholamine in sepsis because it increases blood pressure by increasing myocardial contractility and vasoconstriction. Dopamine has been described to have dose-related receptor activity at DAj-, DA2-, fi -, and i-receptors. Unfortunately, this dose-response relationship has not been confirmed in critically ill patients. In patients with septic shock, there is a great overlap of hemodynamic effects even at doses as low as 3 mcg/kg per minute. Tachydysrhythmias are common owing to the release of endogenous norepinephrine by dopamine entering the sympathetic nerve terminal. Dopamine may increase the PAOP through pulmonary vasoconstriction. This drug also may depress ventilation and worsen hypoxemia in patients dependent on the hypoxic ventilatory drive. 

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. ... 

Terlipressin, a prodrug converted into lysine vasopressin, has been used recently in septic shock patients." This drug has a half-hfe of 6 hours and acts via vascular receptors aud reual tubular V2 receptors. In one report, terlipressin 1 mg was given intravenously to 15 patients with norepinephrine-resistant septic shock."" Terhpressin was shown to increase MAP at 30 minutes, which lasted for 24 hours. Despite a decrease in cardiac output, terlipressin increased gastric mucosal perfusion, urine output, and creatinine clearance. These preliminary findings suggest that a clinical trial should be conducted that evaluates mortality, in addition to hemodynamic effects. 

Martin C, Viviand X, Arnaud S, et al. Effects of norepinephrine plus dobutamine or norepinephrine alone on left ventricular performance of septic shock patients. Crit Care Med 1999 27 1708-1713. 

De Backer D, Creteur J, Silva E, Vincent JL. Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock Which is best Crit Care Med 2003 31 1659-1667. 

Groeneveld AB, Girbes AR, Thijs LG. Treating septic shock with norepinephrine. Crit Care Med 1999 27 2022—2023. 

Redl-Wenzl EM, Armbruster C, Edelmann G, et al. The effects of norepinephrine on hemodynamics and renal function in severe septic shock states. Intensive Care Med 1993 19 151-154. 

Martin C, Papazian L, Perrin G, et al. Norepinephrine or dopamine for the treatment of hyperdynamic septic shock Chest 1993 103 1826-1831. 

Sharma VK, Dellinger RP. The International Sepsis Forum s controversies in sepsis My initial vasopressor agent in septic shock is norepinephrine rather than dopamine. Crit Care 2003 7 3-5. 

Duranteau J, Sitbon P, Teboul JL, et al. Effects of epinephrine, norepinephrine, or the combination of norepinephrine and dobutamine on gastric mucosa in septic shock. Crit Care Med 1999 27 893-900. 

Seguin P, Bellissant E, Le Tulzo Y, et al. Effects of epinephrine compared with the combination of dobutamine and norepinephrine on gastric perfusion in septic shock. Clin Pharmacol Ther 2002 71 381-388. 

Zhou SX, Qiu HB, Huang YZ, et al. Effects of norepinephrine, epinephrine, and norepinephrine-dobutamine on systemic and gastric mucosal oxygenation in septic shock. Acta Pharmacol Sin 2002 23 654-658. 

O Brien A, Cl p L, Singer M. TerUpressin for norepinephrine-resistent septic shock. Lancet 2002 359 1209-1210. 

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