New studies attempt to resolve the issue.
Background: Traditionally, vasopressors have been given through central venous catheters (CVCs) in the critically ill. However, the time it takes to place a CVC, the patient is left potentially hypotensive. Early initiation of vasopressors may be associated with reduced mortality by increasing end-organ perfusion. Therefore, there has been a growing trend to use vasopressors through peripheral IVs (PIVs).
Running vasopressors through a peripheral IV has a couple of important benefits including shorter time to pressor initiation, and limiting invasive procedures (i.e. CVC). Historically there has been limited evidence to support the safety of this practice other than one systematic review, which included case reports and small case series). More recently however, two recent papers have been published to evaluate this very question…are the use of peripheral vasopressors safe?
First is the paper by Tian DH et al 2019,[1] which was a systematic review evaluating the safety of delivering vasopressor medications via peripheral IV access. The primary outcome they were trying to evaluate was adverse events related to the use of peripheral vasopressors (i.e. extravasation, skin necrosis, limb ischemia, compartment syndrome, infection, and any other reported complications that required treatment). Seven trials warranted the author’s inclusion criteria with 1,382 patients and 1,436 episodes of perippheral vasopressor administration.
The two most commonly administered vasopressors were norepinephrine (702 cases) followed by phenylephrine (546 cases). Impressively, the mean duration of infusion was 22 hours (Range: 8 to 36 hours). The primary outcome (extravasation events) was documented in 35 cases, which gives an event rate of 3.4%
Interestingly if you look at Table 3 of the paper, there were 38, not 35 events out of 1,434, not 1,436 infusions, which would give an extravasation rate of 2.6%, not 3.4%). More importantly, there were no reported cases of tissue necrosis or limb ischemia. The majority of extravasation events were managed conservatively or with vasodilatory medications.
Before everyone gets excited, all the included studies were observational or case series without comparison groups (i.e. no randomized clinical trials). Six of the seven trials were single center studies, five of the seven studies were unclear regarding consecutiveness of their patient inclusion, and finally three of the seven studies did not report competing interests.
With all that said, this study makes it reassuring that the rate of extravasation events is quite low (2.6 – 3.4%) when using peripheral vasopressors, with the caveat that the quality of the studies included were not that great. More importantly we need to remember that the use of peripheral vasopressors is a bridge to something else and not intended for prolonged infusion. This would either mean the patient improves and comes off vasopressors or does not improve in which case a midline catheter or central venous catheter should be placed.
Clinical Take Home Point of Paper #1: There is clearly a need for further high-quality research in this area. Until that time, the practice of peripheral vasopressors appears to make pragmatic sense to help expedite time to vasopressor infusions. If using this practice, there should be clinical monitoring protocols and protocols for management of extravasation as the adverse event rate is not zero.
The second paper is by Pancaro C et al 2019,[2] which was a multicenter, retrospective cohort study of a perioperative database from the Netherlands. The authors wanted to estimate the rate of occurrence of drug-related adverse effects (i.e. skin necrosis requiring medical or surgical management) when dilute norepinephrine (20ug/mL) peripheral extravasation occured, in patients undergoing elective surgery under general anesthesia.
Over 14,000 patients who received norepinephrine via peripheral continuous infusion were included in this study. Amazingly, drug extravasation was only observed in five patients (i.e. 0.035%)! This would equate to one to eight events/10,000 patients. And even more impressively there were zero related complications requiring surgical or medical intervention (i.e. none to two events/10,000 patients).
This paper has gotten lots of traction in the social media world. However, to be fair, looking at the extravasation events more closely, it is important to point out that these solutions were dilute (0.02 to 0.05 ug/kg/min, short duration (range 20 to 25 minutes), small volume (1.67 to 4mL), with a limited amount (33 to 80ug) of norepinephrine extravasated. This is not the same dosing, volume, concentration, or duration of vasopressor run through of most patients in the emergency department.
To take this one step further, critically ill patients are different than elective surgical patients. Hypotension can affect tissue perfusion and the effect of extravasation in critcally ill patients. Patients are monitored much more closely in the OR setting than what is possible in critically ill patients in the ED or even ICU. IV placement is more difficult in critically ill patients, which means they have more potential to have extravasation.
Lastly, the incidence of peripheral vasopressor extravasation in critically ill patients is higher than what is quoted in this study (i.e. three to six percent)[1,3] of non-critically ill patients, but the incidence of tissue damage is also low.
Clinical Take Home Point of Paper #2: In this study, the use of diluted norepinephrine administered by peripheral IV did not result in any complications requiring surgical or medical intervention. However, these were small, diluted doses of norepinephrine. Therefore it is not surprising that we are not seeing skin necrosis. It is impossible to extrapolate the results of this study to critically ill patients.
So is it safe to use peripheral vasopressors in critically ill patients?
In patients who are critically ill and requiring vasopressor treatment, the use of peripheral IVs is relatively safe with several caveats:
- Use an antecubital fossa or more proximal IV (These are generally larger veins, which allow for larger IVs (i.e. 18g)
- Choose the longest catheter possible (Ensure you get as much catheter as possible in the vein)
- Do not run the infusion for > two to four hours
- Use as dilute a concentration and yet as small a volume as possible (i.e. 4mg/250mL concentration)
- Have an IV observation protocol
- Have an extravasation protocol
References:
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- Tian DH et al. Safety of Peripheral Administration of Vasopressor Medications: A Systematic Review. EMA 2019. PMID: 31698544
- Pancaro C et al. Risk of Major Complications After Perioperative Norepinephrine Infusion Through Peripheral Intravenous Lines in a Multicenter Study. Anesth Analg 2019. PMID: 31569163
- Loubani OM et al. A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters. J Crit Care 2015. PMID: 25669592
