By Arzo Hamidi, PharmD, BCCCP
Clinical Pharmacy Specialist, Adult Critical Care, Rush University Medical Center, Chicago
SYNOPSIS: Peripheral administration of norepinephrine has a low risk of extravasation if following an operationalized protocol.
SOURCE: Yerke JR, Mireles-Cabodevila E, Chen AY, et al. Peripheral administration of norepinephrine: A prospective observational study. Chest 2024;165:348-355.
Administration of vasoactive medications typically has required a central venous catheter (CVC) to avoid adverse effects, such as extravasation. The use of these central lines may increase complications, such as the risk of infection. For this reason, historically, norepinephrine use has been delayed until a CVC has been placed. This study was a prospective observational cohort study. A written protocol was developed with a multidisciplinary team, including criteria for peripheral intravenous venous (PIV) catheter size, placement, ultrasound confirmation, and dose and duration of norepinephrine infusion. The primary outcome was the number of central line days avoided per patient. Secondary outcomes included the incidence of extravasation events, the number of CVC placements avoided, and the degree of tissue injury caused by each extravasation event.
The protocol was updated three times but in its final version had the following requirements: 18-, 20-, or 22-gauge PIV, PIV aspiration to assess blood return every two hours with patency checks, PIV placement above the wrist but below antecubital fossa and confirmed via ultrasound, and a maximum dose of norepinephrine of 15 mcg/minute.
In this study, 635 patients were included. The median dose was 10 mcg/minute, although 15% of patients did receive higher than this dose peripherally. The median duration of use was 5.8 hours, but 20% of patients received it for more than 24 hours. Overall, 51% of patients did not require CVC placement. The median number of CVC days avoided was one day. Extravasation occurred in 5.5% of patients, but most events were minor (grade 0 or 1 according to the Infusion Nurses Society Infiltration Scale).
COMMENTARY
This large observational study used a protocol created by a multidisciplinary team and was updated after review by an intensive care unit (ICU) committee. Education was provided to nursing and staff providers, which the authors cited as the reason they were so successful with implementation of their protocol. With the amendments to the protocol, it is important to note a maximum duration requirement was removed (48 hours in a prior protocol version).
Overall, nonadherence to the protocol occurred in about half of the patients, but the deviations were short-term and mostly during times when an additional PIV had to be placed. For patients who had extravasation events, protocol nonadherence was not more likely than for those who did not have such events. The authors also explained that although the reported extravasation rate of 5.5% may be concerning, overall it still is low. This incidence rate may be due to frequent monitoring required by the protocol with checks every two hours, thereby increasing the likelihood of detection of extravasation. It also is important to note that for those who did have extravasation events, about half of these patients required a CVC placement even though most extravasation events were not serious. A CVC potentially could continue to be avoided in these situations with replacement of a PIV instead.
In patients who did receive a CVC, the time to place a line was very short, with a median time of 3.6 hours. Since it was up to provider discretion who received a CVC, higher-risk patients may have received a CVC sooner, which decreased the rate of extravasation in the study. Lastly, application of this study’s results to real-world practice also is limited by the use of norepinephrine at a specific concentration of 16 mg/250 mL (64 mcg/mL) and without the use of any other vasoactive agents via PIV. Different institutions may have different concentrations of norepinephrine that are more dilute or more concentrated that also would affect results. Different institutions also may allow other vasoactive agents via PIV, but extrapolation to do so may not be determined from this study.
In summary, this study implemented a protocol to allow for peripheral norepinephrine administration to prevent or delay CVC placement. In this single-center study, overall rates of extravasation were low, but the number of CVC days avoided also was low. In the 127 patients who used norepinephrine for more than 24 hours, the median duration of use was 42 hours. In these patients, the overall extravasation rate was 8.7%, which was higher than for those who received it for less than 24 hours (4.7%). However, the incidence rate per 1,000 days was lower in those who received it for more than 24 hours compared to those who used norepinephrine for less than 24 hours (33.8 [16.9-60.4] days vs. 176 [113.1-262.5]). Future studies should assess similar practices with varying doses, durations, and PIV requirements to evaluate the safety of the use of vasoactive agents via PIV.
