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A 71-year-old man with mild left ventricular dysfunction is undergoing a hip arthroplasty under spinal anesthesia and propofol sedation. The resident has started a norepinephrine infusion at 0.06 µg/kg/min through a 20-gauge peripheral intravenous (IV) catheter placed in the patient’s hand. Based on a recent study, what is the MOST likely rate of extravasation in this patient with perioperative administration of norepinephrine through a peripheral IV?
(A) Less than 1% X
(B) 1% to 5% ✔
(C) Greater than 5% X
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Concerns regarding the use of peripherally administered vasopressors include the risk of extravasation and tissue injury. Thus, it has been recommended that administration of these medications should be via central venous access. However, many of the studies that investigated the prevalence and severity of adverse events related to peripheral administration were published prior to 1970, possibly limiting their generalizability to current practice. Additionally, concentrated forms of phenylephrine (10 mg/mL) and epinephrine (1 mg/mL) have been used for intentional subcutaneous administration, suggesting a significant margin of safety for subcutaneous exposure to these specific medications. Recent evidence has shown that peripheral infusion of vasoactive drugs (even over multiple days) can be safely performed given appropriate monitoring; however, most of these studies focused on critically ill patients.
To investigate the risk of adverse events with peripherally administered norepinephrine during surgery, a recent prospective observational cohort study from Sweden looked at the prevalence of extravasation and other adverse events in 1,004 patients at 3 hospitals from 2019 to 2022. To target those who were more likely to receive a vasopressor, patients were considered for the study if they were 18 years of age or older, underwent general or neuraxial anesthesia, did not have a central venous catheter at the start of surgery, and had any of the following characteristics: American Society of Anesthesiologists physical status of III or greater; estimated surgical time of more than 2 hours; acute, vascular, open abdominal, kidney, spine, or shoulder surgery. If a norepinephrine infusion was initiated during the perioperative period, then the patient was included in the study. Catheter placement was considered distal or proximal based on its location relative to the antecubital fossa or popliteal fossa.
The intraoperative initiation of norepinephrine was based on physician assessment. Norepinephrine was generally used for prophylaxis during induction and as a rescue medication in patients with unexpected hypotension that could not be resolved with intermittent ephedrine. Both 8 µg/mL (80% of patients) and 40 µg/mL (20% of patients) norepinephrine concentrations were used without limitation of dosage. Although both direct and crystalloid carrier–mediated administration were employed, no other medications were given through the venous access site that was used for the norepinephrine infusion. The infusion site was inspected by a nurse every 30 minutes to detect swelling or skin pallor; if either was detected, the infusion was interrupted and switched to a different peripheral venous catheter. Observation was continued until the peripheral infusion was terminated due to blood pressure normalization, 24 hours of infusion time, or central line placement.
The primary outcome of extravasation, which was defined as visible swelling around the infusion site, was observed in 23 patients (2.3%; 95% CI, 1.4–3.2). All the extravasation events were transient, with complete remission within 24 hours without the need for subcutaneous phentolamine treatment. No cases of severe adverse events, such as tissue necrosis, were observed. Notably, paleness of the skin (which was not counted as an adverse event) was more common than extravasation (n = 87; 8.7%; 95% CI, 6.9–10.4) and triggered transfer of the infusion to another site. A plurality of patients in the study had norepinephrine infused through a 20-gauge catheter (n = 435; 43.3%), and most had the catheter placed in the hand (n = 715; 71.3%). Proximal catheter placement was associated with higher rates of complications compared with distal placement (6.3% [n = 8 of 126] vs 2.5% [n = 21 of 833], respectively). Overall, the extravasation rate in this study was found to be in agreement with prior studies in critically ill populations.
In summary, this multicenter, prospective, observational cohort study found that in the setting of careful monitoring, peripheral norepinephrine infusion was associated with an extravasation rate of 2.3% and no cases of tissue necrosis or the need for subcutaneous phentolamine treatment. Furthermore, distal catheter placement may be preferred given an increased risk of extravasation with infusion via proximal veins.
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Date of last update: July 9, 2025
