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Vasopressin or Norepinephrine to Avoid Kidney Failure After Septic Shock?

LONDON, UK – Early vasopressin use has been proposed as an alternative to norepinephrine in treating septic shock to avoid kidney failure. A new study, however, didn’t find an increase in the number of kidney failure-free days with that approach.

The research, published recently in JAMA, sought to compare the effect of early vasopressin vs. norepinephrine on kidney failure in patients with septic shock.

To do that, a study team led by Imperial College London researchers conducted a double-blind, randomized clinical trial in 18 general adult intensive care units in the United Kingdom between February 2013 and May 2015. Enrolled were 409 adult patients, median age 66 years and 58.2% male, who had septic shock requiring vasopressors, despite fluid resuscitation within a maximum of six hours after the onset of shock. The median time to study drug administration after diagnosis of shock was 3.5 hours.

For the study, patients were randomly allocated to vasopressin (titrated up to 0.06 U/min) and hydrocortisone; vasopressin and placebo; norepinephrine and hydrocortisone; or norepinephrine and placebo.

Researchers looked to quantify the number of kidney failure–free days during the 28-day period after randomization. That was measured as the proportion of patients who never developed kidney failure as well as the median number of days alive and free of kidney failure for patients who did not survive, who experienced kidney failure, or both. Secondary outcomes included rates of renal replacement therapy, mortality, and serious adverse events.

Results indicate that 57% of survivors in the vasopressin group and 59.2% in the norepinephrine group never developed kidney failure.

Meanwhile, the median number of kidney failure–free days for patients who did not survive, who experienced kidney failure, or both was nine in the vasopressin group and 13 in the norepinephrine group.

Researchers note less use of renal replacement therapy in the vasopressin group than in the norepinephrine group — 25.4% for vasopressin vs. 35.3% for norepinephrine — and no significant difference in mortality rates between groups was detected.

Overall, 10.7% of patients had a serious adverse event in the vasopressin group compared to 8.3% in the norepinephrine group, the study points out.

“Among adults with septic shock, the early use of vasopressin compared with norepinephrine did not improve the number of kidney failure–free days,” study authors conclude. “Although these findings do not support the use of vasopressin to replace norepinephrine as initial treatment in this situation, the confidence interval included a potential clinically important benefit for vasopressin, and larger trials may be warranted to assess this further.”

Background information in the article notes that, in 2015, an estimated 230,000 cases of septic shock occurred in the United States, leading to more than 40,000 deaths.