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Jeon K et al. "Incidence of hypotension according to the discontinuation order of vasopressors in the management of septic shock: a prospective randomized trial". Critical Care. 2018. 22(131):1-12.
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Clinical Question

In adult patients admitted to critical care with septic shock, does tapering vasopressin before norepinephrine lead to less hypotentive events during convalescence.

Bottom Line

Tapering vasopressin first may be associated with less hypotension than if norepinephrine is tapered first during the weaning process.

Major Points

Stopped early due to benefit

Guidelines

As of November 2018, no guidelines have been published that reflect the results of this trial.

Design

  • single-centre, prospective, randomized, double-blind, controlled trial
  • N=78
    • Norepinephrine tapered first (n=38)
    • Vasopressin tapered first (n=40)
  • Setting: University-affiliated, tertiary referral hospital in Seoul, South Korea
  • Enrollment: January 2012 to February 2014
  • Mean follow-up:
  • Analysis: Modified intention-to-treat
  • Primary Outcome: Incidence of hypotension within 1 hour of tapering first vasopressor

Population

Inclusion Criteria

  • ≥20 years old
  • admitted to medical ICU
  • septic shock
  • receiving concomitant norepinephrine (NE) and vasopressin (AVP)
  • Mean Arterial Pressure (MAP) ≥65 mmHg for at least 2 h after reducing NE to 0.3 mcg/kg/min while maintaining AVP of 0.03 U/min

Exclusion Criteria

  • terminally ill patients classified as “do not resuscitate”
  • patients who were suspected to have AVP deficiency (e.g. hypothalamic–pituitary–adrenal axis dysfunction, empty sella syndrome)
  • acute myocardial infarction
  • congestive heart failure

acute mesenteric ischemia

  • treated with vasopressors other than NE and AVP

Baseline Characteristics

  • Demographics: age 66 years, 63% male,
  • Cause of septic shock: pneumonia 50%, intraabdominal infection 28%, urogenital infection 21%, catheter related infection 6%, endocarditis 3%, other 4%
  • Physiologic parameters: initial MAP 52 mmHg, initial CVP 7 mmHg, SAPS3 74, SOFA 10
  • Anthropomorphics: Weight
  • Labs: total bilirubin 1.05 mg/dL, serum creatinine 1.34 mg/dL, lactic acid 3.6 mmol/L, procalcitonin 12.7 ng/mL, CRP 13.96 mg/mL

Interventions

  • taper vasopressin first
  • taper norepinephrine first

Outcomes

Comparisons are vasopressin first vs. Norepinephrine first.

Primary Outcomes

Hypotension within one hour after tapering of vasopressor
23% vs. 68% (ARR 45%); P<0.001 NNT 2

Secondary Outcomes

Subgroup Analysis

Adverse Events

Criticisms

Funding

Further Reading


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