Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock – The VANISH Randomized Clinical Trial

Hazel Lacson, Mercer University College of Pharmacy

According to the Centers for Disease Control and Prevention (CDC), sepsis is defined as the body’s overwhelming and life-threatening response to infection.1  Sepsis can lead to tissue damage, organ failure, and death.  As per the Infectious Disease Society of America (IDSA) guidelines for sepsis, norepinephrine is the first-choice vasopressor to maintain a mean arterial pressure (MAP) ≥ 65 mmHg.2

Vasopressin levels in septic shock have been reported to be lower than anticipated.  Low doses of vasopressin may be effective in raising blood pressure in patients.2

Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial3
Design Factorial (2×2), multi-center, double-blind, randomized; N = 409
Objective To compare the effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock
Study Groups Vasopressin and hydrocortisone (n = 101), vasopressin and placebo (n = 104), norepinephrine and hydrocortisone (n = 101), or norepinephrine and placebo (n = 103).
Methods Patients were allocated to receive either vasopressin (titrated up to 0.06 U/min) or norepinephrine (titrated up to 12 μg/min) as the initial vasopressor infusion. Once the maximum infusion rate of vasopressin or norepinephrine was reached, patients received either 50 mg of hydrocortisone phosphate or placebo every 6 hours for 5 days, every 12 hours for 3 days, and then once daily for 3 days. If the patient was still hypotensive after the first dose of study drug 2 then additional open-label catecholamine vasopressors could be administered.
Duration February 2013 to May 2015
Primary Outcome Measure Kidney failure–free days during the 28-day period after randomization

 

Baseline Characteristics   Vasopressin + hydrocortisone (n=101) Vasopressin + placebo (n=104) Norepinephrine + hydrocortisone (n=101) Norepinephrine + placebo (n=103) Total trial population (n=409)
Median age, years 66 67 63 66 66
Men, No. (%) 59 (58) 52 (50) 62 (61) 65 (63) 238 (58)
Results   Vasopressin Norepinephrine
Hydrocortisone Placebo Hydrocortisone Placebo
28-day survivors who never developed kidney failure, No./total (%) 46/81 (56.8) 48/84 (57.1) 46/77 (59.7) 47/80 (58.8)
28-day mortality, No./total (%) 33/100 (33) 30/104 (28.8) 29/101 (28.7) 27/103 (26.2)
Kidney failure, No./total (%) 41/101 (40.6) 46/104 (44.2) 46/101 (45.5) 51/103 (49.5)
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: digital ischemia, mesenteric ischemia, life-threatening arrhythmia, acute coronary syndrome
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions The early use of vasopressin compared with norepinephrine did not improve the number of kidney failure–free days in adults with septic shock.

The VANISH randomized clinical trial was heavily influenced by the Vasopressin and Septic Shock Trial (VASST).4  The difference being VASST compared mortality rates, while VANISH observed the number of kidney free days in sepsis patients on either vasopressin or norepinephrine.  Both studies came to the same conclusion that use of vasopressin was not superior in comparison to norepinephrine, in patients with septic shock.  Despite this, another aspect that could be given more attention could be time of administration.  It was stated in the VANISH trial that patients were randomized for the study, at maximum, six hours after hypotension had manifested.3  Additionally, it was noted in the VASST study that patients whose treatments were initiated within the first 12 hours responded better to vasopressin than norepinephrine.4  Further studies regarding the correlation of a shorter time to administration of vasopressin versus norepinephrine in septic shock patients could provide valuable insight.

 

References

  1. Centers for Disease Control and Prevention. http://www.cdc.gov/sepsis/index.html. Accessed August 9, 2016.
  2. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580-637.
  3. Gordon AC, Mason AJ, Thirunavukkarasu N, et al. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial. JAMA. 2016;316(5):509-18.
  4. Russell JA, Walley KR, Singer J, et.al; VASST Investigators. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358(9):877-887.

 

 

 

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