iPhoneIcon_Big-34Peripheral noradrenaline (or norepinephrine), or any peripheral pressor, is shunned in many centers. High doses can cause gangrene. If extravasated, it can cause tissue necrosis. But is this a big risk? Also, weighing against the risks of CVC or delayed pressor start-up – what’s the best approach? I work in a teaching hospital where short-term noradrenalin infusions are fully acceptable, and the norm in many settings – but other places I’ve worked, it’s a big no-no. Recently, we got a systematic review on the subject.

Our local practice
In our teaching hospital, we’ve used low dose peripheral noradrenaline (NA) for many years, and several times a week. We use noradrenaline peripherally both in critical patients while waiting to get a central line going, and we use it as our standard route in surgical patients that need a little pressor support for 1-2 hours in the OR, and don’t have a CVC.

The way we prefer to do it is to get a small cannula (pink or blue) in a good vein. A big vein is good, but we’ll also use a smaller vein on the hand or foot if necessary. There should be no problems during insertion, and flushing that cannula should be easy and feel perfect. We also want it to be in a place that can easily be inspected during the operation. Nothing but noradrenaline should run on that cannula, and we only use our lowest standard concentration (0,02mg/ml) in these peripheral cannulas, and mark the line well.

The site needs regular inspection. And any sudden fall in BP should elict a check of NA infusion site for extravasation, not mindlessly turning up the infusion rate.

The complications are extravasation which can lead to tissue necrosis, as well as extravasation halting pressor delivery and crashing your patient if dependent on high dose pressor. So for high dose pressor, CVC should be a priority.

This image of tissue necrosis after extravasation lurks in the back of your head when considering peripheral NA infusion. From BJM Case Reports.

I have never seen any major complications from extravasation with peripheral NA during my years in our hospital. I’ve heard of a few extravasations, some with tissue injury, and anecdotal cases requiring surgical intervention. So beware of these complications, but also remember other drugs can cause tissue necrosis, but are commonly used for peripheral infusion without strict observation protocols. Examples include propofol and thiopentone.

I believe or apparently low complication rate can be attributed to short infusion duration, low dosing and low concentration NA combined with frequent checking of the infusion site.

Systematic review
So, local practice is one thing. This is empirical and undocumented evidence on a rather small scale, but still important. What can a systematic review bring to the table? Unfortunately, there isn’t much good evidence out there. The review is mainly based on many case reports and case series. Impressive article searching. Most of the articles are from the 50s and 60s, and many of them are on patients with long duration of peripheral NA infusions: 24-48hours and quite a few over several days, and often with high doses. Of course, these case reports are written when things go wrong. But they’re still an important collection of evidence of the potential dangers of peripheral vasopressor infusion. Also, there are differences between vasopressors. We have focused on noradrenaline in this blog post.

Findings and discussion
The case reports and articles are published when things go wrong. So this review reports on adverse events from NA infusion, from both CVC and PIV. Of course, comparing them, or looking at incidences, makes no sense as these are mainly case reports. But the review might still offer som useful insight.

One interesting – although not surprising – finding in this review, is how complications from peripheral pressor extravasation increase over time used in the same peripheral cannula. We all know peripheral cannulas fail eventually, and the consequences can be worse if there’s pressors going on that cannula.

graph piv pressor

This figure corresponds to the experience at our teaching hospital, and how we use this: we use peripheral noradrenaline for short periods of time. Either for planned operations where the patient needs a little BP support for 1-2 hours, or for starting noradrenaline peripherally in critically ill patients, until we get a central line in place. From the above figure, this seems safe. 96.8% of adverse events in the review occurred after 4 hrs of infusion, and, actually, up to 6 hours seem safe, judging from the review.

Also, the review finds that 85% of adverse events occured with distal PIVs, distal to the knee or elbow. However, the vast majority of cannulas are also inserted distal to the knee or elbow, so I don’t think this number is very helpful. As mentioned, in our hospital, we frequently use distal sites (hand or foot) for NA infusions. Also keep in mind that the majority of tissue injuries and many of the extravasations of vasopressors resulted in no long-term sequelae.

The review recommends peripheral NA infusions to be done through larger/more central veins like in the antecubital fossa or external jugular vein, this seems more like good, common sense than supported by current evidence. They also conclude that peripheral pressor with a duration of less than 2 hours seem safe.

Final note
We use peripheral NA. And comparing the risk of extravasation to the risk of CVC complications in an elective surgical patient, I think I would take the peripheral low dose norad – although both risks are quite small. In the critical patient, I would also opt for early pressor with the risk of peripheral extravasation, rather than the risk of hypoperfusion while waiting for a central line.

Having this procedure gives us a lot of flexibility, and also lets us start norad early in emergencies as well. We never wait for a central line or put one in emergent under non-sterile conditions only for pressor needs. We start it peripherally, put in the central line in a sterile controlled procedure, and shift over the infusion.

Take home message from our department’s long experience is that peripheral noradrenaline infusion is considered safe, as long as you use it in a new and perfectly working cannula in a good vein, with a low concentration of noradrenaline at a low infusion rate and you check the site often. Most importantly: use it for a limited time only, as all peripheral cannulas will fail, eventually. 1-2 hours seems to be well within the safe window in our experience, and is supported by the limited literature available.


A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters., J of Crit Care, June 2015.

Challenging medical dogma: a systematic review of peripheral vasopressor administration, CJEM, 2013.

Also, check out Emcrit’s post on the subject, peripheral pressors, including more on extravasation, here.

A good primer om extravasation and treatment.

You can, of course, also look at scare tactics from the nay-sayers in BMJ case reports, showing a scary photo of extravasation, but failing to mention infusion time, how long the cannula’s been in place or the NA infusion concentration. Their references are case reports from the 50s and 60s with patients receiving huge NA doses peripherally, up to 180mg(!), over periods of 48hours to 5 days(!). Yes, there are risks, but as with any procedure or intervention, you need to know its indications and limitations.

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  1. LeGazier says:

    Very good point!!
    I also use peripheral norepinephrine in my teaching hospital.
    The concentration used is 1ml = 0,01 micrograms/kg/min (weight of patient x 3 then divided by 100)
    I agree on using a dedicated canula for NA and clamping it with tape + marking it to prevent mistaking it for another canula and flushing it with other drugs (hypertension + bradycardia then arrest)
    I’ve never seen an extravasation nor a tissue necrosis when using norepinephrine peripherally.
    We use it in the same contexte you do: peroperatively when patients need hemodynamic support, even during induction of anaesthesia to prevent BP fall or in critically ill patients when we don’t have time to put in a CVC or to wait till CVC is done.

    Too bad there’s no good evidence on this, but it’s nice hearing that we’re not the only one doing it safely!

  2. Fredrik Granholm @TotalResus says:

    Good post!
    We use it in our ED ( county hospital 44000 visits/yr) mostly for septic chock patients who haven’t got their cvc yet.
    Haven’t seen any complications but we ( our nurses) follow checklists to catch any extravasation. We alse have the possibility to give Regitin/Fentolamine in case of extravasation. Use a lot of push dose epi and sometimes “dirty epi” as well in pvc.

  3. Casey says:

    Thanks for that review
    I agree.
    Similar experience here, though less data
    Podcast on the topic here:
    There is a trade off between safety – a few hours of peripheral pressor vs a cv catheter placed in emergency scenario
    In my part of the world this often means a cvc done by an occasional operator with no support.
    A good IV in the arm seems like a safe option

  4. …I worry more about inadvertent volume run through or flush of line dead space without appreciation of the contents. Always use diluted form…and swap to CVC ASAP, skillmix and appropriate timing, of course

    • Thomas D says:

      This touches on an important aspect: Like most changes, the peripheral norad infusion is not something to do on your own – there needs to be a system in place, and an understanding on all levels of health care workers at all depts that might come in touch with patients like these.

      I think in our hospital where it’s part of our routine and well-known to all anaesthetists and anaesthetic/recovery/ICU nurses, there’s little risk of flushing the NA line. They’re all experienced and comfortable with handling peripheral pressors.

      Flushing NA has happened, though, but usually leads to nothing more than a sharp increase in BP and reflex bradycardia. It’s over in minutes. This is not to downplay the potential lethal dangers, but that’s how it’s played out the very few times I’ve seen/heard it done.

  5. Sebastian says:

    Its common use at our hospital too. We use our standard concentration of 0,1mg/ml Norepinephrine because we don´t want to switch between concentrations. Way too much space for errors imho!
    By sop it runs with a saline perfusor, not alone. This way we can be sure to get it inside fast enough and the cannula can be flushed and used for other uses afterwards.

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  8. mati ullah says:

    very good
    we also use in our teaching hospital
    still did not see any comlpication

    dilute 4 mg in 250 ml=
    0.04 mcg/kg/min

  9. Neo Wen Yang says:

    How long do you guys run peripheral dopamine for, compared to duration for peripheral norepinephrine?

  10. Dan T says:

    We’ve started running noradrenaline on our Intermediary Care ward in Southern Sweden. Have been running up to 0,2mcg/kg/min so far without problem although we run slightly higher concentration norad (0,04mcg/ml) through a three-way tap with 20mls/hr carrier fluid alongside.
    Wondered how you guys are switching – when one syringe is finished and you need to start a new one (quick switch ok given low dose?), but also when you have placed a central line and want to start there (double pumping?). Appreciate any tips!

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