Selepressin shows promise in septic shock management
The novel V1A-selective vasopressin receptor agonist selepressin may be an effective substitute for the traditional vasopressor norepinephrine in patients in early septic shock, a recent study has found.
In this double-blind multicentre trial, 53 patients in early septic shock were randomized to receive one of three ascending infusion rates of selepressin (1.25 ng/kg/min [n=10], 2.5 ng/kg/min [n=19], or 3.75 ng/kg/min [n=2]) or placebo (n=21) until shock resolution or a maximum 7 days.
At 24 hours, more patients given 2.5 ng/kg/min selepressin (about 70 percent) maintained a mean arterial pressure (MAP) of >60 mmHg without norepinephrine compared with those on 1.25 ng/kg/min selepressin (<20 percent) and placebo (20 percent).
Compared with placebo, use of selepressin 2.5 ng/kg/min resulted in the rapid reduction of norepinephrine mean infusion rate (0.04 vs 0.18 μg/kg/min at 24 hours), reduction of cumulative net fluid balance from day 5 onwards (p<0.05), and a higher proportion of days alive and free of ventilation (54 percent vs. 23 percent; p<0.02). [Crit Care 2017;doi:10.1186/s13054-017-1798-7]
“[A]t an infusion rate of 2.5 ng/kg/minute, [selepressin] rapidly replaced norepinephrine while maintaining target MAP and may have improved fluid balance and shortened the time of mechanical ventilation,” said the researchers.
“Reducing the dose of norepinephrine … could in itself be advantageous because it could decrease the adverse effects of norepinephrine … [and] have beneficial effects on fluid balance and vascular leak,” they said.
The greater proportion of patients weaned off norepinephrine during the first 24 hours and the decreased mean cumulative norepinephrine dose demonstrate rapid onset and sustained activity, suggesting selepressin to be a potent vasopressor, noted the researchers.
Furthermore, the reduced mechanical ventilation period reflects selepressin’s potential in mitigating the risks associated with long periods of mechanical ventilation such as nosocomial pneumonia, neuromuscular weakness, and mortality, they added.
As this was the first inpatient trial of selepressin in septic shock patients and owing to the small sample size which could have limited the overall impact, more investigation is warranted to evaluate the potential of selepressin in improving treatment outcomes in septic shock patients, said the researchers.
The ongoing SEPSIS-ACT* trial is assessing the superiority of rapid and full substitution of norepinephrine with selepressin over cotreatment with selepressin and norepinephrine, noted the researchers.
“[T]he potential additional benefits of selepressin compared with vasopressin … may justify earlier use and fuller substitution of norepinephrine with selepressin,” they said.