Singh O, Juneja D. Navigating the veins: A comprehensive review of vasoactive agent infusion via peripheral routes. World J Crit Care Med 2026; 15(2): 118811 [DOI: 10.5492/wjccm.v15.i2.118811]
Corresponding Author of This Article
Deven Juneja, MD, Director, Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, 1 Press Enclave Road, New Delhi 110017, India. devenjuneja@gmail.com
Research Domain of This Article
Critical Care Medicine
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Share the Article
Singh O, Juneja D. Navigating the veins: A comprehensive review of vasoactive agent infusion via peripheral routes. World J Crit Care Med 2026; 15(2): 118811 [DOI: 10.5492/wjccm.v15.i2.118811]
Author contributions: Singh O and Juneja D contributed to conceptualization of the review, data accusation, writing, and reviewing the manuscript; both the authors have read and approved the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Deven Juneja, MD, Director, Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, 1 Press Enclave Road, New Delhi 110017, India. devenjuneja@gmail.com
Received: January 12, 2026 Revised: January 17, 2026 Accepted: February 9, 2026 Published online: June 9, 2026 Processing time: 129 Days and 22.6 Hours
Abstract
Peripheral venous catheters (PVCs) are almost always present in patients in the intensive care unit. Still, they are seldom used to administer vesicant or irritant drugs, including vasoactive agents, due to concerns about extravasation and local tissue injury. However, emerging evidence indicates that PVCs are safe and effective for this purpose, offering distinct clinical advantages and obviating the need for more invasive central venous catheter insertion. Implementing a standardized protocol to ensure the appropriate size and placement of PVC, optimizing the dosage and duration of vasopressors, and establishing vigilant nursing monitoring can facilitate the safe administration of vasopressors via PVC, with substantial implications for the early management of shock, particularly in resource-constrained settings.
Core Tip: Central venous catheters (CVCs) are traditionally used to transfuse vasopressors. However, their insertion is costly, time-consuming, requires expertise and may be associated with serious complications like bleeding and pneumothorax. Emerging evidence suggests that peripheral venous catheters (PVCs) can be safely and effectively used to administer vasopressors. Even though this may help with the rapid initiation of vasopressors and sometimes avoid the need for CVC insertion, the use of PVCs may also lead to minor complications from extravasation of vasopressors. By adopting a safety protocol that includes measures such as careful selection of insertion site and PVC size, limiting the dose and duration of vasopressors, and vigilant monitoring of the infusion site, complications may be further reduced. Safe use of vasopressors via PVCs may have far-reaching clinical implications for managing early septic shock, especially in resource-limited settings.
Citation: Singh O, Juneja D. Navigating the veins: A comprehensive review of vasoactive agent infusion via peripheral routes. World J Crit Care Med 2026; 15(2): 118811
Critically ill patients frequently require vasopressor support to manage shock. Traditionally, central venous catheters (CVCs) are inserted to transfuse vasopressors. However, CVC insertion is costly, time-consuming, requires expertise and may be associated with mechanical complications like local trauma, bleeding and pneumothorax[1]. Further, long-term CVC insertion is also associated with complications like catheter-associated bloodstream infection and venous thrombosis and embolism. These may adversely affect patient outcomes, leading to increased length of stay and higher costs[2]. Hence, several safer options, such as midline catheters and peripheral venous catheters (PVCs), are being explored to minimize the use of CVCs[3].
PVCs are almost always present in intensive care unit (ICU) patients and are commonly used to administer intravenous fluids, antibiotics and other supportive medications. However, it has limited utility when vesicant or irritant drugs, such as hyperosmolar agents (parenteral nutrition, concentrated glucose solution), chemotherapeutic agents, concentrated potassium, and vasoactive agents, are being transfused, as extravasation of these agents may lead to severe local complications, such as tissue necrosis and compartment syndrome[4,5]. Thus, when these agents are required, CVCs are generally preferred over PVCs.
CVCs were also recommended in the previous surviving sepsis campaign (SSC) guidelines to monitor the central venous pressure to assess fluid responsiveness and to measure central venous oxygen saturation levels to evaluate the balance between oxygen delivery and consumption[6]. However, these interventions were subsequently shown to have no beneficial impact on the patient outcomes and hence are no longer recommended by the subsequent SSC guidelines[7]. Consequently, the utility of CVC insertion in early management of septic shock has diminished, leading to a renewed interest in managing patients with PVCs, particularly during the early phase of septic shock and in resource limited settings (RLS). PVC insertion may not only reduce the cost and complications associated with CVC insertion but may also reduce the time needed to initiate vasopressors in patients with shock, which may be particularly useful in such scenarios[8-10]. The SSC also recommends initiating vasopressors promptly via PVC, rather than waiting for CVC insertion[7]. Further, studies have shown that protocol guided use of PVCs for vasopressor infusion can avoid CVC placement in more than 50% patients[11].
In recent years, PVCs are increasingly being used for administration of vasopressors. A secondary analysis of the Crystalloid Liberal vs Early Vasopressors in Sepsis (CLOVERS) trial revealed that the initiation of vasopressors via PVC is a prevalent practice, observed in 84.2% of cases[12]. However, the data concerning feasibility, safety and adverse effects of using PVCs to administer vasoactive drugs remains sparce. Most of the studies evaluating the outcomes and safety of administering vasoactive drugs through PVCs are retrospective in nature, are single center or have a small sample size, limiting their applicability and generalizability. Additionally, the absence of international guidelines regarding the safe use of PVCs for vasopressor transfusion further limits their widespread applicability. Therefore, this narrative review aims to evaluate the available literature on the utility and safety of PVCs for vasopressor transfusion.
COMPLICATIONS
The risk of complications associated with the use of PVCs for vasopressor infusion depends on the type, duration, and dose of vasopressors; hence, different studies have reported varying rates of common complications such as extravasation, thrombosis, and infection (Table 1)[5,8-10,13-25]. The risk of complications is negligible when PVCs are used for short periods of time, like in the perioperative period. A large retrospective study analyzing data from 14385 perioperative patients admitted in hospitals in Netherlands, reported a low complication rate of 0.035%, indicating a low estimated risk of complications (1-8 events/10000 patients)[26]. On the other hand, the reported risk of minor complications, such as erythema, leakage, or extravasation, may be as high as 41% in critically ill patients; hence, appropriate precautions must be instituted in these patients[27].
Table 1 Summary of recent trials evaluating the complications associated with transfusion of vasoactive agents through peripheral intravenous catheters, median (25th-75th percentiles).
As most of these studies are single-center and have small patient cohorts, generalizing from them might be difficult. In a comprehensive meta-analysis that encompassed data from 9 studies and involved 1835 patients, a low incidence of complications associated with vasopressor administration via PVCs was reported. The analysis identified 122 complications (7%), of which 117 (96%) were categorized as minor[28].
Another meta-analysis by Owen et al[29] included 11 studies involving 16055 patients and reported an adverse event rate of 1.8%. Notably, the majority of these events were mild, with only two serious events. The serious events included one instance of thrombophlebitis and one instance of ischaemia with skin necrosis. All these events were successfully managed with conservative measures[29].
The most recent meta-analysis, analyzing data from 19 studies including 6,852 patients across 10 countries, again reported low overall rates of extravasation (1.43%), thrombosis (1.47%), and infection (0.72%) with the use of PVC. However, this review included not only peripheral cannulas but also peripherally inserted central catheters and midline catheters, which may have impacted the results and affect generalizability. Hence, the authors concluded that traditional PVCs should be used only for vasopressor infusion for a short period or in emergencies[30].
It is stipulated that as PVCs are less invasive, they may be associated with fewer complications as compared to CVCs. However, studies comparing complication rates associated with CVCs and PVCs are limited. A multicenter, open-label, randomized trial conducted in three French ICUs reported that the rates of major catheter-related complications and complications per patient may be significantly higher in patients managed solely with PVCs than in those managed with CVCs[31].
Extravasation injuries are arguably the most commonly reported adverse effect of vasopressor administration through PVC, with a reported incidence of 0.4%-5%[16,25]. The extravasation of vasoactive agents may cause local tissue injury secondary to their vasoconstrictive effects[4,5]. Extravasation injuries are generally mild and limited to localized erythema and swelling of the limb, which may resolve completely with conservative measures[28-30].
Serious complications like compartment syndrome, secondary to extravasation of drug through PVCs, have been reported rarely[32,33]. These are generally more common in pediatric patients and resolve completely with no long-term deficits. Very rarely, patients have been reported to develop persistent deficits or require radical surgical intervention, including limb amputation[34].
Although most reported complications associated with PVC (extravasation, phlebitis, leakage, and dislodgement) are non-infectious, PVC may rarely become infected, leading to local infection at the injection site or progressing to bloodstream infection (PVC-BSI)[35]. Phlebitis is common and, if not timely recognized, may lead to infection; however, it is not always a precursor to infection. Hence, the presence of phlebitis is not an indication for initiating antibiotics[36]. The reported incidence of PVC-BSI ranges from 0.5 to 0.7 per 1000 catheter days and may lead to increased patient mortality[37,38].
PREVENTION OF COMPLICATIONS
The adoption of peripheral vasopressors is on the rise. A recent international survey, INFUSE, conducted among ICU pharmacists from 132 institutions revealed that 86% of respondents used PVCs for vasopressor administration in their ICUs[39]. Hence, it is important to better understand factors that may increase the risk of complications and to institute measures to prevent and manage them.
Preventing complications largely depends on taking appropriate precautions during PVC insertion and maintenance. Judicious site selection is of paramount importance and may help in reducing complications (Table 2)[35,40,41]. To have a greater impact, it may be prudent to develop and adapt a comprehensive safety protocol for the infusion of vasoactive agents through PVCs, as studies that adopted safety guidelines had a significantly lower prevalence of complications[28]. Even before and after studies have demonstrated a substantial reduction in extravasation events (2.4% compared to 1.1%) and a concomitant enhancement of safe peripheral infusion practices following the implementation of a safety protocol[42]. However, due to the lack of comprehensive international guidelines, many hospitals still lack formal policies, which hamper the use of PVCs for vasopressor infusions. A survey conducted in the United States found that, despite numerous hospitals implementing their own policies and protocols, there is a lack of consistency, resulting in substantial variation[43].
Table 2 Practical considerations for peripheral intravenous catheter placement.
Sites to avoid
Reason/comment
Dominant upper extremity
Movement may lead to patient discomfort and increase risk of dislodgement
Sites over joints
Increased risk of catheter kinking or dislodgement
Lower extremities
Increased risk of thrombophlebitis and deep venous thrombosis due to static blood flow
Extremities with arteriovenous fistula
Inserting a catheter may disturb the venous blood flow or damage the fistula
Burns or infected tissue
Increased risk of systemic infection
Evidence of sclerosis or phlebitis
This may be indicative of disrupted venous integrity and a higher risk of extravasation
Sites where catheter was recently placed or attempted (especially in the presence of hematoma)
This may be indicative of disrupted venous integrity and a higher risk of extravasation
Size and site of PVC, as well as dose, duration, and type of vasopressors, may all impact the incidence of complications[44]. A previous systematic review reported that 85% of extravasations happened when the PVC was placed distal to the antecubital fossa[4]. A study by Nguyen et al[21] also reported that peripheral administration of noradrenaline at a maximum dose of 20 μg/minute, delivered through a PVC tube of 18 gauge or greater placed at or above the antecubital fossa or the external jugular vein, can be instrumental in reducing complications[21]. However, data from a meta-analysis suggest that there may be no statistical difference in complication rates between sites or sizes of IV lines[29]. The SSC guidelines, nonetheless, suggest employing a larger vein located in the upper limb, proximal to the antecubital fossa for safe administration of vasopressors[7].
Determining the safe dosage and duration of vasopressors presents a complex challenge, as the quality of studies, patient populations, dose reporting, and safety protocols employed vary significantly[44]. The SSC recommends restricting the use of PVCs for vasopressor infusions to a maximum duration of 6 hours[7]. However, data from the CLOVERS trial have shown that in the majority of cases (57.2%), vasopressor administration was safely continued beyond the suggested 6-hour duration, and only mild complications at a rate of 0.6% were reported[12]. Recently, a multicenter prospective study reported that none of the extravasation injuries occurred in patients who took vasopressor for less than 5 days, with peak noradrenaline concentration of 1 mcg/kg/minute at a mean infusion rate of 0.3 mcg/kg/minute. This suggests that vasoactive medication administration via a peripheral line is safe for up to 4 days with respect to the risk of extravasation[14].
It remains unclear whether all vasoactive medications exhibit identical risk profiles when administered peripherally[44]. The most commonly studied vasopressor is noradrenaline; hence, data on peripheral infusion of other vasopressors remain scarce[29]. Therefore, the maximum dosage and duration for different vasopressors have yet to be defined, with studies reporting varying doses and durations (Table 3)[9,10,45]. Because the risks of complications associated with different vasopressors are uncertain, many hospitals restrict the administration of specific vasopressors via PVCs, per their local policies. A comprehensive survey revealed that vasopressin was the most frequently prohibited vasopressor, followed by adrenaline[43]. However, a recent meta-analysis found no significant difference in adverse events across vasopressor types or their duration of use[29].
Table 3 Studies reporting maximum dosage and duration for different vasopressors, mean ± SD.
Further, vigilant nursing monitoring of the vasopressor infusion site is paramount to ensure timely recognition of any complications. It is suggested that nursing protocols should include routine examination of the region proximal and distal to the infusion site for any signs suggestive of leakage, including oedema, discoloration, skin injury, or vesicular eruptions. It is recommended that, in critically ill patients, sedated patients, and those receiving irritant or vesicant medications, the PVC site should be inspected at a frequency of 1-2 hours[46]. Nevertheless, current data indicate that only 63% of centers implementing protocols for safe vasopressor infusion via PVC include nurse monitoring of the intravenous site as a component of their protocol[43].
Based on the current literature, several measures have been suggested by various authors to reduce the risk of adverse effects associated with vasopressor infusion through PVCs, as shown in Table 4[9,44]. Targeted interventions using a bundled approach may also be effective in reducing the incidence of PVC-BSI and improving patient outcomes[47,48].
Table 4 Measures to ensure safe use of peripheral venous lines.
Avoidance of high-risk sites
Upper extremity only (avoiding joints)
Large size vein
Choosing vein with diameter more than 4 mm (to be measured using ultrasound)
High bore cannula
Intravenous line size 20 gauge or 18 gauge
Confirmation of cannula position
Using ultrasonography, position of cannula should be ascertained before initiating vasopressors
Check backflow
Blood return should be checked before initiation of vasopressors
Evaluation of PVC function
PVC function should be assessed regularly (every 1-2 hours)
Staff education and training
Close monitoring of PVC site for any signs/symptoms suggestive of complications
Managing complications
Standardized protocol for managing extravasation
Short duration of therapy
PVC use should be limited to a maximum of 72 hours
Urgent recognition of any local complication and stopping the infusion of the offending drug is the first obvious step.
Specific measures
Local phentolamine injection is the treatment of choice for extravasation of vasopressors. Phentolamine is a selective alpha-blocking agent that has been well described as effective in reversing tissue ischemia in the face of alpha-adrenergic drug extravasation[49,50]. It increases the median effective dose for vasospasm in the presence of sympathetic amines[51]. It produces a greater increase in capillary blood flow during adrenoreceptor-mediated vasoconstriction, thereby maintaining tissue perfusion[52]. Phentolamine is administered at a dose of 5-10 mg, diluted in 10-15 mL of saline, and infiltrated subcutaneously around the extravasation site. Data on the efficacy of phentolamine in cases of vasopressin extravasation are limited; therefore, it is safer to administer vasopressin only through a CVC catheter. Other agents have also been tried, depending on the offending vasopressor (Table 5).
Table 5 Different treatment options for management of extravasation of various vasoactive agents.
Use of topical nitroglycerin ointment has also been shown to be useful in pediatric cases and hence has been adapted for use in adult patients too in selected cases[9,53,54].
FUTURE DIRECTIONS
Data on the safety of peripheral vasopressor infusion are primarily based on retrospective cohorts or single-center observational studies. Because serious complications are rare, information on their diagnosis and management has primarily been derived from case reports and series. Hence, there is a need to conduct large-scale, multicenter randomized controlled trials to compare the safety and efficacy of vasopressor infusions via PVCs with those via CVCs. The maximum safe dosage and duration of vasopressors, as well as the size and site of PVCs, also need to be verified. Additionally, data regarding vasopressors other than noradrenaline is even more sparse, as they are less commonly prescribed. Therefore, future studies should address the safety of other vasopressors when infused through PVCs.
CONCLUSION
PVCs may be safely used for the administration of vasopressors, especially in the early management of septic shock and in RLS. However, specific measures must be instituted to ensure its safety, including the insertion of a large-bore cannula, avoiding high-risk sites, and prescribing low-dose vasopressors for a short duration. Nonetheless, it is imperative to closely monitor PVCs for complications and to have a standardized protocol in place for early recognition and management of extravasation events.
Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Hylander Møller M, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021.Crit Care Med. 2021;49:e1063-e1143.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 2220][Cited by in RCA: 1827][Article Influence: 365.4][Reference Citation Analysis (3)]
Petros A, Melkie A, Kotiso KS, Kebede D, Oljira CF, Assefa Gemechu F, Yusuf H, Abebe S, Ashagre A, Bekele A, Yohannes A, Etesa EK, Bedru M, Gebremariam TH. Peripheral line for vasopressor administration: Prospective multicenter observational cohort study for survival and safety.PLoS One. 2025;20:e0333275.
[RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)][Cited by in RCA: 4][Reference Citation Analysis (0)]
Christensen J, Andersson E, Sjöberg F, Hellgren E, Harbut P, Harbut J, Sjövall F, von Bruhn Gufler C, Mårtensson J, Rubenson Wahlin R, Joelsson-Alm E, Cronhjort M. Adverse Events of Peripherally Administered Norepinephrine During Surgery: A Prospective Multicenter Study.Anesth Analg. 2024;138:1242-1248.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 7][Cited by in RCA: 13][Article Influence: 6.5][Reference Citation Analysis (0)]
Asher E, Karameh H, Nassar H, Yosefy C, Marmor D, Perel N, Taha L, Tabi M, Braver O, Shuvy M, Wiener-Well Y, Glikson M, Bruoha S; Jerusalem Platelets Thrombosis and Intervention in Cardiology (JUPITER-16) Study Group. Safety and Outcomes of Peripherally Administered Vasopressor Infusion in Patients Admitted with Shock to an Intensive Cardiac Care Unit-A Single-Center Prospective Study.J Clin Med. 2023;12:5734.
[RCA] [PubMed] [DOI] [Full Text][Cited by in RCA: 16][Reference Citation Analysis (0)]
Fabick AC, Hawn JM, Barwick KW, Weeda ER, Goodwin AJ, Bell CM. Comparison of extravasation events related to the peripheral administration of vasopressors prior to and following implementation of an institutional protocol.J Am Coll Clin Pharm. 2023;6:709-717.
[PubMed] [DOI] [Full Text]
Thompson J, Steinheiser MM, Hotchkiss JB, Davis J, DeVries M, Frate K, Helm R, Jungkans CW, Kakani S, Lau S, Lindell K, Landrum KM, McQuillan KA, Shannon DJ, Wuerz L, Pitts S. Standards of care for peripheral intravenous catheters: evidence-based expert consensus.Br J Nurs. 2024;33:S32-S46.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 7][Cited by in RCA: 11][Article Influence: 5.5][Reference Citation Analysis (0)]
