Shock norepinephrine with vasopressin

A 45-year-old female presented with febrile neutropenia secondary of chemotherapy. The patient quickly decompensated to refractory septic shock in the critical care unit despite implementation of early goal-directed therapy as well as intravenous norepinephrine and vasopressin to stabilise her haemodynamic status. She received a 16-h infusion of 1% methylene blue 0.25 mg, titrated up... 

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)... 

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. 

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. 

Vasopressin levels in patients with vasodilatory shock are inappropriately low, and such patients are extraordinarily sensitive to the pressor actions of vasopressin. The combination of vasopressin and norepinephrine is superior to NE alone in the management of catecholamine-resistant vasodilatory shock. Although the efficacy of vasopressin in the resuscitation of patients with ventricular fibrillation or pulseless electrical activity is similar to that of epinephrine, vasopressin followed by Epi appears to be more effective than Epi alone in the treatment of patients with asystole. 

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