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