Norepinephrine was recommended as the first vasopressor for septic shock resuscitation. For the patient who did not response to high dose norepinephrine, epinephrine was recommended. Vasopressin was also recommended as an alternative vasopressor, in case patient did not response to norepinephrine and or epinephrine. Terlipressin, a selective V1 receptor binding with long half life, was reported that it main action is to increase blood pressure via the different mechanism from norepinephrine and epinephrine. To use terlipressin, combine with norepinephrine and or epinephrine among refractory septic shock, could decrease the usage dose of norepinephrine and epinephrine as well as lower the side effects of too high adrenergic stimuli.
Norepinephrine was recommended as the first vasopressor for septic shock resuscitation. For the patient who did not response to high dose norepinephrine, epinephrine was recommended. Both norepinephrine and epinephrine action via the alpha adrenergic stimuli to increase vascular smooth muscle contraction, induced vasoconstriction and increase arterial blood pressure. It also action via beta adrenergic stimuli, to increase heart rate and myocardial contractility, then increase stroke volume and cardiac output. Too much alpha and beta adrenergic stimulation, especially during received high dose norepinephrine and or epinephrine associated with vasoconstriction induce organs ischemia. The most common organ ischemia included myocardial ischemia, bowel ischemia and limbs ischemia. Cardiac arrhythmia was also the most common complication associated with high dose norepinephrine and or epinephrine. Atrial fibrillation was the most common reported arrhythmia, however, fatal arrhythmia included ventricular fibrillation and tachycardia were also reported. Vasopressin was recommended as an alternative vasopressor, in case patient did not response to norepinephrine and or epinephrine. Terlipressin, a selective V1 receptor binding with long half life, was reported that it main action is to increase blood pressure via the different mechanism from norepinephrine and epinephrine. To use terlipressin, combine with norepinephrine and or epinephrine among refractory septic shock, could decrease the usage dose of norepinephrine and epinephrine as well as lower the side effects of too high adrenergic stimuli. The benefit effect of terlipressin could be demonstrated when prescribe among the septic shock patients who required high dose of adrenergic vasoactive agents. Terlipressin plus norepinephrine and or epinephrine could maintain or even improve blood pressure and tissue perfusion with lower fatal side effects than norepinephrine and or epinephrine without terlipressin.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
130
Terlipressin (20-100 mcg/hr) plus norepinephrine and/or epinephrine
0.9% NaCl plus norepinephrine and/or epinephrine
Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University
Bangkok, Thailand
RECRUITINGAchieve target blood pressure with low dose adrenergic agents
Achieve target mean arterial blood pressure 65 millimeter mercury or more with norepinephrine and/or epinephrine dose 0.2 mcg/kg/min or lower
Time frame: 6 hours after initiate study drug
28 day mortality
Proportion of patient who dead before 28 days after enrollment
Time frame: 28 days
Mean arterial blood pressure
Mean arterial blood pressure after initiate study drug
Time frame: 72 hours
Hospital mortality
Proportion of patient who dead before hospital discharge after enrollment
Time frame: 90 days
ICU mortality
Proportion of patient who dead before ICU discharge after enrollment
Time frame: 90 days
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