Another Study on Peripheral Vasopressors

Background: Use of vasopressors is a common practice to support hemodynamics and optimization of tissue perfusion in patients presenting with shock.  Historically the administration of vasopressors was restricted to central venous catheters (CVC) due to concerns for local tissue injury resulting from vasoconstriction if extravasation occurred from a peripheral IV. The placement of CVCs, however, can delay vasopressor initiation, can cause procedural complications, and potentially result in bloodstream infections. The 2021 Surviving Sepsis Campaign Guidelines suggest starting vasopressors peripherally rather than delaying infusion until a CVC is placed [2]. Despite multiple studies published showing the safety of peripheral vasopressors, the recommendation is considered a weak based on low-quality evidence.

Paper: Yerke JR et al. Peripheral Administration of Norepinephrine: A Prospective Observational Study. CHEST 2024. PMID: 37611862

Clinical Question: In patients treated in the ICU, can a protocol of peripheral IV catheter vasopressors safely reduce the number of days of CVC use and frequency of placement?

What They Did:

  • Prospective, observational, cohort study
  • Conducted in medical ICU at a single institution
  • Evaluating all adult patients admitted to the medical ICU receiving norepinephrine through a peripheral IV from Feb 2019 through June 2021

Peripheral Norepinephrine Protocol

  • 20 to 22G IV above the wrist below the antecubital fossa
  • US guided IV (Catheter in the lumen and visualization of flushing with NS)
  • Norepinephrine concentration 16mg/250mL D5W
  • Maximum dose norepinephrine 15mcg/min
  • Peripheral IV assessment q2hrs with blood aspiration
  • Extravasation antidotes (SQ phentolamine and nitroglycerin paste) stocked in the unit for extravasation events
  • Peripheral IV norepinephrine infusion was limited to 48hrs to limit total number of extravasation events, but due to few extravasation events and no substantial tissue injury, this requirement was removed


  • Primary: Number of days of CVC use avoided per patient
  • Secondary:
    • Incidence of extravasation events
    • Number of CVC placements avoided
    • Degree of tissue injury caused by each extravasation event


  • Adult patients admitted to the medical ICU at the Cleveland Clinic
  • Received peripheral norepinephrine during the study period
  • Met specific criteria laid out in protocol (SEE PROTOCOL ABOVE)
  • Inclusion at discretion of treating physician


  • Other vasoactive medications that typically require a CVC for administration were not allowed to be given peripherally in the study
  • Not meeting inclusion protocol criteria (SEE PROTOCOL ABOVE)


  • 635 patients received peripheral norepinephrine
    • 603 patients received norepinephrine via peripheral IV as 1st exposure
    • 32 patients transitioned from receiving norepinephrine from CVC to receiving it via peripheral IV to allow CVC removal
    • Median maximum peripheral administered norepinephrine dose: 10mcg/min (range 6 to 15)
    • 130 patients (20.5%) received peripheral norepinephrine for ≥24 hours
    • Infusion duration: 5.8hrs (Range 2 to 19.7hrs)
  • Median number of CVC days avoided per patient: 1 (Range 0 to 2d/pt)
    • 0f 603 patients who received norepinephrine peripherally, 311 (51.6%) never required CVC insertion
  • Extravasation occurred in 35 patients (5.5%):
    • 8 events/1000d of peripheral IV infusion (95% CI 52.8 to 105.4 events/1000d of peripheral IV infusion)
    • 60% of extravasations caused no or minimal tissue injury (Infiltration grade 0 to 1)
    • No patient required surgical intervention
  • Protocol Criteria Met:
    • 355 patients (55.1%) failed to meet at least one component of the protocol at some point during peripheral IV norepinephrine
      • Catheter size: 83.3% (i.e. Not met in 16.7% of cases)
      • Catheter location: 66.5% (i.e. Not met in 33.5% of cases)
      • Catheter ultrasound confirmation: 49.8% (i.e. Not met in 50.2% of cases)
      • Appropriate vasopressor dose: 84.3% (i.e. Not met in 15.7% of cases)
    • ≤24hrs vs >24hrs
      • Infusion Duration: 3.8hrs vs 42.4hrs
      • Max Dose: 10mcg/min vs 10mcg/min
      • Extravasation Events: 24 (4.7%) vs 11 (8.7%)
      • Extravasation incidence/1000d of Peripheral Infusion: 176.4 vs 33.8
    • No Extravasation Event vs Extravasation Event
      • Age: 63 vs 67 years
      • BMI: 28.3 vs 27.0
      • All Catheter Criteria Met: 44.3% vs 54.3%
      • Infusion Duration: 5.5hrs vs 13.8hrs
      • Protocol adherence and adherence to individual protocol elements were not lower in patients experiencing extravasation


  • Asks a clinically important question
  • Largest prospective cohort study of patients receiving peripheral norepinephrine
  • Transparent reporting of protocol amendments
  • Describes a real world clinical experience of using vasopressors through a peripheral IV
  • Patients on substantial norepinephrine doses
  • Comprehensive protocol explicitly explained allows other physicians to use in different settings


  • Despite rigorous education there was a high rate of protocol deviations (Although most were short-term nonadherence while additional peripheral IVs were being placed)
  • Single center trial limits generalization of results to all practice settings
  • No comparator group making it difficult to assess all possible benefits and harms of administering norepinephrine through a peripheral IV vs a CVC
  • Protocol was not mandatory for all patients which could create a selection bias
  • Multiple protocol amendments during the study making it difficult to determine whether similar results would be obtained using any one protocol version (Which components were most important?)
  • Potential for selection bias as one of the inclusion criteria was physician discretion
  • CVC placement at discretion of clinicians and reasons for placing CVC multifactorial and may have nothing to do with peripheral vasopressors


  • There are some key components of the protocol that limited extravasation harms in my opinion:
    • Ultrasound to ensure appropriate peripheral IV placement
    • Routine line assessment (including aspiration to assess blood return)
    • Limiting the maximum dose of norepinephrine to 15mccg/min
    • Extravasation bundle
  • My extravasation bundle
    • If extravasation occurs, stop the infusion and switch it to a different line
    • Leave the catheter in place and suck out as much as you can from the catheter
    • Use phentolamine or terbutaline (Whichever you have available):
      • Phentolamine
        • 5mg/mL x2 in 8mL of NS (Max 10mg)
        • Inject 5mL through catheter
        • Inject remaining 5mL in the SQ tissue (Around the blanching area)
        • Unclear what time frame is optimal for re-dosing (Typically wait 1hr)
      • Terbutaline
        • 1mg/mL in 9mL of NS
        • Inject 5mL through catheter
        • Inject remaining 5mL in the SQ tissue (Around the blanching area)
        • Can repeat every 15min as needed
      • Nitroglycerin Paste
        • Apply 1inch of paste to affected area
        • Can repeat every 8hrs
      • Elevate the extremity
      • Use warm compresses (Be careful to not burn the skin)

Author Conclusion: “This study suggests implementing a protocol for peripheral administration of norepinephrine safely can avoid 1 CVC in the average patient, with 51.6% of patients not requiring CVC insertion.  No patient experienced significant ischemic tissue injury with the protocol used.  These data support performance of a randomized, prospective, multicenter study to characterize the net benefits of peripheral norepinephrine administration compared with norepinephrine administration through a CVC.”

Clinical Take Home Point: Administration of norepinephrine through a peripheral IV is feasible and may reduce the frequency of CVC insertions without significant extravasation-related harms.


  1. Yerke JR et al. Peripheral Administration of Norepinephrine: A Prospective Observational Study. CHEST 2024. PMID: 37611862
  2. Evans L et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med 2021. PMID: 34599691

For More Thoughts on This Topic Checkout:

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter/X: @EMSwami)

Cite this article as: Salim Rezaie, "Another Study on Peripheral Vasopressors", REBEL EM blog, February 19, 2024. Available at:

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