Is there literature on the max dose and concentration of pressors for peripheral administration?

Comment by InpharmD Researcher

As standardized maximum dosages and concentrations for peripheral vasopressor use have not been established, available data is limited to reviews and observational studies with varying reported dosages. One retrospective chart review reported a maximum norepinephrine (NE) dosage range of 41-60 mcg/min, which resulted in higher rates of extravasation and phlebitis, although these cases were considered manageable. However, there have been reports of NE dosages of 2-48 mcg/min resulting in extravasation and local tissue injury. Norepinephrine and phenylephrine concentrations have been expressed as 8 mg/250 mL and 40 mg/mL, respectively. Additionally, another review article described phenylephrine at 2.521 mcg/kg/min with mostly minor complications. Although specific to one health system, guidance for vasopressor maximum concentration and rates is shown in Table 1. However, authors noted that the guidance did not define the standard of care.

Background

A 2021 review evaluated the safety of peripheral intravenous (PIV) administration of norepinephrine (NE) in the surgical setting for the prevention of frequently seen perioperative complications such as hypervolemia and hypotension. The risk of peripheral infiltration and tissue injuries, including extravasation and necrosis, are rare but commonly associated with PIV vasopressor administration. Evidence of tissue injury was shown to be more likely with distal IV administration over prolonged periods. Reported extravasation events occurred following ≥12 hours of NE infusion. Based on this evidence, NE is recommended to be administered as a low-dose infusion for a limited duration between 6 to 12 hours based upon provider discretion. Recommended conditions for PIV NE administration include IV-gauge size (18 to 20 gauge), NE concentration (≤4 to 8 mg in 250 mL), proximal PIV administration, and IV site monitoring every 2 hours. The authors concluded that norepinephrine can likely be given as a peripheral infusion safely in surgical patients when the listed conditions above are met. [1]

A 2015 systematic review assessed peripheral and central administration of vasopressors, including the incidence of extravasation and local tissue injury identified after administration. Data were collected from 85 studies on vasopressor administration, comprising 80 case studies, 1 randomized controlled trial, and 4 case series. Notably, no included studies directly evaluated rates of tissue ischemia or extravasation associated with central or peripheral catheter use. Among the studies, norepinephrine was utilized in 74.5% of patients, and was administered peripherally in 75.6% of cases; norepinephrine was also the most commonly administered in instances of local tissue injury and extravasation. Doses of norepinephrine reported in incidents of local tissue injury (80.4%) and extravasation (64.9%) were 2-48 mcg/min and 2-40 mcg/min, respectively. The average infusion duration prior to local tissue injury events and extravasation were 55.9 and 35.2 hours, respectively, though this data is not specific to norepinephrine administration. In many tissue injury event cases (85.3%), peripheral administration was conducted distal to the antecubital or popliteal fossae. As published data is mainly derived from case reports, more robust data is required to substantiate safety with peripheral norepinephrine administration. [2]

A recent retrospective chart review was conducted on all consecutive patients who received phenylephrine infusion through a peripheral intravenous catheter (PIV) in a tertiary care hospital neurocritical care unit. The average duration of peripheral phenylephrine infusion was 22 hours and 37 minutes (range 2 hours and 40 minutes to 91 hours and 58 minutes). The average rate of phenylephrine infusion was 0.64 mcg/kg/min (range 0.155 to 2.521 mcg/kg/min), with a peak infusion rate of 3.06 mcg/kg/min and an average total dose of 69,528.5 mcg (range 2,325 to 325,725 mcg).There were reported to be 6.4% of patients with a minor complication and 1 major complication (0.8%). Of the minor complications reported, 4.8% had local skin erythema/swelling, and 1.6% had IV infiltration (extravasation without tissue injury). The one major complication was thrombophlebitis, which resolved rapidly with removal of the PIV, heat application, and elevation; the patient experienced a complete recovery without any permanent sequela. There were no reported IV site blisters, extravasation with tissue injury, skin necrosis or tissue necrosis, gangrene, or limb ischemia. [3]

A 2019 single-center, retrospective chart review of 202 patients who received vasopressors through a PIV describes various vasopressors administered peripherally, including phenylephrine and associated extravasation events. Among different vasoactive agents, phenylephrine was the second most common vasopressor administered peripherally (36%) with a median duration of 15 hours. While the study institution stocked phenylephrine at 400 mcg/mL, two patients received a diluted compounded infusion with a concentration of 20 mcg/mL. The initial dose of phenylephrine was 50 mcg/min, with a median initial and maximum dose of 25 mcg/min and 95 mcg/min, respectively. The primary outcome of extravasation occurred in 8 (4%) patients during the time that a vasopressor was administered via a PIV, three of which were confirmed with detailed notes. The study reported that 4 patients received phenylephrine at the time of extravasation. [4]

A 2016 pilot study describes a 6-month experience with peripheral administration of low-concentration phenylephrine (40 mcg/mL) in a neurological care unit involving 22 patients. The mean duration of peripheral infusion was 14.29 hours (range, 1 to 54.3) with a mean dose of 0.53 mcg/kg/min, up to the dose limit of 2 mcg/kg/min. There were no documented major complications related to PIV in the entire sample, and only 1 minor complication reported as pain, erythema, and swelling around an 18-gauge antecubital infusion site, which was successfully managed with a new IV line. The authors highlighted the need for additional safety measures and nurse-drive safety protocols to ensure safe PIV of phenylephrine. [5]

References:

[1] French WB, Rothstein WB, Scott MJ. Time to use peripheral norepinephrine in the operating room. Anesthesia & Analgesia. 2021;133(1):284-288. doi:10.1213/ANE.0000000000005558
[2] Loubani OM, Green RS. A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters. Journal of Critical Care. 2015;30(3):653.e9-653.e17. doi:10.1016/j.jcrc.2015.01.014
[3] Ballieu P, Besharatian Y, Ansari S. Safety and Feasibility of Phenylephrine Administration Through a Peripheral Intravenous Catheter in a Neurocritical Care Unit. J Intensive Care Med. 2021;36(1):101-106. doi:10.1177/0885066619887111
[4] Lewis T, Merchan C, Altshuler D, Papadopoulos J. Safety of the Peripheral Administration of Vasopressor Agents. J Intensive Care Med. 2019;34(1):26-33. doi:10.1177/0885066616686035
[5] Delgado T, Wolfe B, Davis G, Ansari S. Safety of peripheral administration of phenylephrine in a neurologic intensive care unit: A pilot study. J Crit Care. 2016;34:107-110. doi:10.1016/j.jcrc.2016.04.004
Literature Review

A search of the published medical literature revealed 6 studies investigating the researchable question:

Is there literature on the max dose and concentration of pressors for peripheral administration?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-6 for your response.

Vasopressor Administration through Peripheral Intravenous Access
Vasopressor Maximum Concentration Maximum Rate Recommended
Dopamine 800 mcg/ml 10 mcg/kg/min
Epinephrine 32 mcg/ml 20 mcg/min
Norepinephrine 32 mcg/ml 30 mcg/min
Phenylephrine 160 mcg/ml 200 mcg/min
Vasopressin 20 units/ml 0.04 units/min
Note: This guideline was developed to assist in the delivery of care and is not intended to define the standard of care. Personnel may deviate from this guide to provide appropriate individualized care and treatment for each patient.
 
 
 
 
References:

Adapted from:
McKennan, A. Peripheral Administration of Vasopressors (PIV Access). Published January 25, 2022. Accessed April 2, 2025.

 

Safety of early norepinephrine infusion through peripheral vascular access during transport of critically ill children

Design

Retrospective chart review

N= 37

Objective

To determine the frequency of extravasation and skin injury with norepinephrine administration through peripheral vascular access in children in the prehospital setting

Study Groups

All subjects (N= 37)

Inclusion Criteria

Age ≤18 years at the time of transport; received vasopressor during prehospital transport; documentation of distributive or obstructive shock and administration of norepinephrine through a peripheral catheter (intravenous or intraosseous) during retrieval; transported from January 1, 2015 to December 31, 2017

Exclusion Criteria

Not disclosed

Methods

Two investigators identified patients using the electronic medical records (EMRs) system, and two completed data collection. The two primary data sources were retrieval team records and pediatric intensive care unit records. Data for extravasation and adverse events were coded as present or absent, with imputation of missing values; no documentation of an adverse event was considered an absence of an adverse event.

Duration

January 1, 2015 to December 31, 2017

Outcome Measures

Extravasation occurrence; presence of associated adverse events (i.e. local and regional skin injury or abnormal perfusion)

Baseline Characteristics

  

All subjects (N= 37)

Age, months§

 1.8 (0.03 to 12.7) 

Weight, kg§

 4 (3 to 7)

Male

 24 (65%) 

Type of transport

Primary

Transfer out to tertiary center

 

3 (8%)

34 (92%)

Type of shock

Septic

Hemorrhagic

Tension pneumothorax

Lactate, mmol/L§

Medial fluids, mL/kg§

Mechanical ventilation

 

32 (86.5%)

4 (10.8%)

1 (2.7%)

8.8 (3.6 to 12.9)

45 (20 to 60)

29 (78%)

Additional inotrope

Dobutamine

Epinephrine

 

7 (19%)

3 (8%)

Intravenous infusion site

Hand

Arm

Foot

Scalp

32 (86%)

20 (63%)

8 (25%)

3 (9%)

1 (3%)

Intraosseous infusion site

Proximal tibia

Distal femur

5 (14%)

4 (80%)

1 (20%)

Norepinephrine§

Dose, μg/kg/min

Concentration, μg/mL

Rate, mL/h

Duration, minutes

 

0.3 (0.2 to 0.4)

154 (40 to 245)

0.9 (0.5 to 2)

230 (160 to 270)

§Interquartile range

Norepinephrine concentrations ranged from 10 to 1271 μg/mL, and the maximum dose ranged from 0.03 μg/kg/min to 2.00 μg/kg/min. Most transport times were approximately 20 to 30 minutes, and the median total duration of peripheral norepinephrine infusion was almost 4 hours.

Results

Endpoint

All subjects (N=37)

95% confidence interval
Extravasation* 1 (2.7%) 0.5% to 13%

Local transient skin blanching*

 1 (2.7%) 0.5% to 13%

*One patient (day of life 0 and weighed 2,270 grams) exhibited both extravasation and local transient skin blanching after peripheral intravenous (PIV) norepinephrine. The PIV was a 24-gauge inserted in the left hand, norepinephrine concentrations were 160 μg/mL, and the maximum rate was 0.3 mL/h. The retrieval team documented signs of abnormal tissue perfusion at the injection site 135 minutes after norepinephrine initiation, with suspected extravasation. The PIV was removed and the norepinephrine infusion moved to another peripheral vascular access. The local tissue perfusion reportedly normalized within minutes, and there were no sequelae.

Adverse Events

N/A

Study Author Conclusions

In a 3-year sample of pediatric patients from a large metropolitan area, we found only one patient with evidence of any harm with peripheral administration of norepinephrine. This finding is consistent with the adult literature but requires multicenter and multiyear investigation before a firm recommendation for this practice can be made.

InpharmD Researcher Critique

This review examines a small sample size of pediatric participants. Therefore, further research is needed before generalizing the results of this study to other populations.



References:

Charbel RC, Ollier V, Julliand S, et al. Safety of early norepinephrine infusion through peripheral vascular access during transport of critically ill children. JACEP Open. 2021;2(2):e12395. doi:10.1002/emp2.12395

 

Inadvertent extravasations of norepinephrine

Design

 Case report

Case presentation

A 63-year-old man presented to the emergency department with diabetic ketoacidosis and septic shock. An insulin infusion, fluid resuscitation, and antibiotics were initiated. The correct peripheral intravenous (PIV) cannula positioning was assessed by flushing with 10 mL of normal saline, and norepinephrine infusion (10 mcg/min) was initiated for hemodynamic support through the PIV line. Following hemodynamic stability after 48 hours of norepinephrine PIV infusion, the patient developed a large bulla on the high right forearm around the PIV injection site. A diagnosis of subcutaneous tissue ischemia in the event of inadvertent extravasation of norepinephrine was made and the infusion was discontinued immediately. Extravasation was treated with mechanical debridement of necrotized tissue followed by regular wound dressings.

Study Author Conclusions

For patient management, it is important to grade the severity of extravasation: grade 1 (intact skin), grade 2 (blanched skin, erythema), grade 3 (necrosis/ulceration causing severe tissue damage warranting surgical intervention), grade 4 (life‐threatening warranting immediate intervention), and grade 5 (death).

A detailed protocol for administering PIV norepinephrine should be developed. It should include using a vein >4 mm on ultrasound, using an IV cannula size of 20 or 18 gauge, excluding hand/wrist/antecubital fossa positions, nursing assessing peripheral IV access every 2 hours, and a maximum duration of 72 hours for peripheral IV use.
References:

Pradhan RR. Inadvertent extravasations of norepinephrine. Clin Case Rep. 2022;10(10):e6516. Published 2022 Oct 22. doi:10.1002/ccr3.6516

Safety and Outcomes of Peripherally Administered Vasopressor Infusion in Patients Admitted with Shock to an Intensive Cardiac Care Unit—A Single-Center Prospective Study
Design

Single-center prospective study

N= 1100
Objective To evaluate whether the administration of vasopressors through a peripheral venous catheter (PVC) is a safe and effective alternative for the management of patients with cardiogenic shock (CS) presenting to the intensive cardiovascular care unit (ICCU)
Study Groups

PVC group (n= 108)

CVC group (n= 31)
Inclusion Criteria Age ≥18 years; presented with hemodynamic shock requiring vasopressor administration
Exclusion Criteria Patients <18 years old and pregnant women
Methods Vasopressors were administered via PVC or CVC based on the discretion of the treating physician. Noradrenaline was the primary vasopressor used. The PVC was placed in a vein proximal to the wrist with a 20 G cannula. CVC was inserted under ultrasound guidance. Data were collected prospectively and documented in an electronic case report form.
Duration January 2022 to December 2022
Outcome Measures

Primary: Central-line-associated bloodstream infection (CLABSI), phlebitis, extravasation, bleeding
Baseline Characteristics Characteristic PVC (n= 108) CVC (n= 31)
Age, y 72 ± 12.3 64 ± 19.6
Female sex 35% 32%

Comorbidities

Hypertension

Diabetes mellitus

Hyperlipidemia

Smoking

Prior CAD

CVA

 

68%

43%

51%

15%

42%

9%

 

54%

54%

52%

23%

38%

16%

Shock type

Cardiogenic

Septic

Combined

Hemorrhagic

 

84%

10%

3%

3%

 

90%

0%

6%

0%

Number of vasopressors used

1

2

>2

 

88%

8%

4%

 

48%

42%

10%

Vasopressor

Norepinephrine

Dopamine

Phenylephrine

Vasopressin

Epinephrine

 

95%

9%

6%

5%

2%

 

87%

19%

19%

26%

6%

Norepinephrine dose, mcg/min

1-10

11-20

21-30

31-40

41-60

 

47%

14%

14%

5%

21%

 

19%

7%

15%

11%

48%
Results Complications PVC (n= 113) CVC (n= 31) p-value
Phlebitis 5% 3% NS
Extravasation 1% 3% NS
Line sepsis (number/1000 catheter days) 2.8% 3.3% NS
Bleeding 0 3% NS
Total complications 8% 13% NS

Abbreviations: CAD= coronary artery disease; CVD= cerebrovascular disease; NE= norepinephrine; NS= not significant

Although small, there was a higher rate of local adverse events seen at higher NE doses (41–60 mcg/min) of noradrenaline when compared to lower doses. All cases were managed conservatively.
Adverse Events See Results
Study Author Conclusions The administration of vasopressor infusions via PVC for the management of patients with CS is feasible and safe in patients with cardiogenic shock. Further studies are needed to establish this method of treatment.
Critique The study was not randomized, and the administration of vasopressors was at the discretion of the senior cardiologist, which may have caused a selection bias. The study's primary goal was not to prove the superiority of a PVC over a CVC, but to evaluate the safety and efficacy of the PVC approach. The etiologies leading to the CS were not analyzed, and there was no long-term follow-up.
 
References:

Asher E, Karameh H, Nassar H, et al. 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(17):5734. Published 2023 Sep 3. doi:10.3390/jcm12175734

 

Evaluation of the Safety of a Novel Peripheral Vasopressor Pilot Program and the Impact on Central Line Placement in Medical and Surgical Intensive Care Units

Design

Retrospective chart review

N= 79

Objective

To evaluate the safety and feasibility of peripheral vasopressor administration in an attempt to minimize the placement and improve early removal of unnecessary central lines to reduce central line-associated bloodstream infection (CLABSI) rates

Study Groups

All patients (n= 79)

Inclusion Criteria

Patients who did not require a central venous catheter for other reasons, expected to require low or moderate doses of a single vasopressor for at most 72 consecutive hours

Exclusion Criteria

Patients requiring 2 or more vasopressors, vasculature not supporting 2 peripheral IV sites, peripheral IV site without brisk blood return, limb restrictions

Methods

A standardized institutional guideline was developed and implemented across three intensive care units (ICUs), outlining specified agent-specific maximum peripheral dosing thresholds, including norepinephrine up to 16 µg/min, phenylephrine up to 160 µg/min, vasopressin at 0.03 units/min, and epinephrine up to 0.1 µg/kg/min. Doses exceeding these thresholds or requiring infusion beyond 72 hours triggered central line placement or alternate limb IV access.

Nursing staff conducted standardized hourly site monitoring, with mandatory documentation of infiltration or extravasation events. Extravasation reversal agents were preloaded into automated dispensing cabinets.

Duration

December 2020 to February 2021

Outcome Measures

Primary: Safety of peripheral vasopressor administration, incidence of CLABSIs

Secondary: Impact on central line placement

Baseline Characteristics

Traditional baseline patient characteristics such as age, sex, comorbidities, and severity of illness were not reported. The study included 79 unique patients who received a total of 129 peripheral vasopressor orders across three intensive care units between December 2020 and February 2021. Norepinephrine (n= 67) and phenylephrine (n= 58) were the most frequently administered vasopressors, followed by epinephrine (n= 3) and vasopressin (n= 1).

The average total duration of peripheral administration was less than 72 hours for all vasopressors, with 94 orders administered for less than 24 hours, 25 for 24 to 48 hours, 3 for 48 to 72 hours, and 7 orders administered beyond 72 hours using the alternate limb per protocol. The average maximum doses peripherally administered were 14.9 µg/min for norepinephrine, 119.9 µg/min for phenylephrine, 0.03 units/min for vasopressin, and 0.3 µg/kg/min for epinephrine.

Results

Among the 129 peripheral vasopressor orders analyzed, 23 (17.8%) exceeded the maximum peripheral dose defined by the institutional guideline, and seven orders were administered beyond 72 hours using an alternate limb, as permitted by protocol. Three potential extravasation events were documented, none of which were formally classified as extravasation or required intervention. These events included one instance of phlebitis/erythema and two cases of minor infiltration with skin blanching and edema.

Notably, no adverse events occurred in orders that exceeded the protocol-defined dosing thresholds. Of the 79 patients included, 45 (57%) avoided central line placement due to vasopressor needs. Among the 34 patients who did receive a central line, no CLABSIs were reported. Standardized utilization ratio (SUR) data for central line use demonstrated a trend toward decreased central line utilization in two of the three ICUs during the study period, with statistically significant reductions observed in only three individual data points.

Adverse Events

 Three possible extravasation events were documented, but no treatment was required. No extravasation events were documented when vasopressors were run above the maximum dose stated in the guideline

Study Author Conclusions

In conclusion, our quality improvement project suggests that peripheral administration of select vasopressors at conservative doses and for less than 72 hours is safe. Implementation of a peripheral vasopressor protocol is feasible across multiple ICU settings with guidance documents and frequent monitoring. While trends toward a reduction in central line placement were seen, we encountered confounding variables; in the future, our group aims to further reanalyze the impact of this initiative on central line usage and CLABSI occurrence across ICUs. We also plan to investigate the impact on length of stay in hospital and ICU, mortality, and adherence to Surviving Sepsis Campaign recommendations, where appropriate.

InpharmD Researcher Critique

The study provides initial evidence supporting the safety of peripheral vasopressor administration, but the retrospective design and small sample size limit the ability to draw definitive conclusions. The study was conducted during the COVID-19 pandemic, which may have affected central line utilization. Future studies with larger sample sizes and prospective designs are needed to confirm findings.



References:

Marti K, Hartley C, Sweeney E, Mah J, Pugliese N. Evaluation of the safety of a novel peripheral vasopressor pilot program and the impact on central line placement in medical and surgical intensive care units. Am J Health Syst Pharm. 2022;79(Suppl 3):S79-S85. doi:10.1093/ajhp/zxac144

 

Peripheral Administration of Norepinephrine: A Prospective Observational Study

Design

Prospective, observational, cohort study

N= 635

Objective

To determine whether a protocol for peripheral IV catheter (PIVC) norepinephrine administration can safely reduce the number of days of central venous catheter (CVC) use and the frequency of CVC placement in patients treated in the medical intensive care unit (ICU)

Study Groups

Patients receiving ≤24 hours of norepinephrine (n= 508)

Patients receiving >24 hours of norepinephrine (n= 127)

Inclusion Criteria

Adult patients admitted to the medical ICU receiving norepinephrine through a PIVC

Exclusion Criteria

 Received any other vasoactive medications that require CVC administration

Methods

A written protocol for peripheral norepinephrine administration was developed and approved by the medical ICU physician, pharmacy, and nursing leadership, as well as the local quality committee, which included the criteria for PIVC size, placement location, ultrasound confirmation, assessment for blood return, and limits on norepinephrine dose and infusion duration.

Initially, patients needed to report pain to identify extravasations quickly, and peripheral norepinephrine was limited to 48 hours. After observing few extravasations, these requirements were removed, and instead, a new requirement was added to assess extravasation every 2 hours by pausing the infusion and performing a blood aspiration from the PIVC. Nurses used ultrasound for PIVC placement and performed routine patency assessments, while protocol adherence was based on standards from the Infusion Nurses Society.

The norepinephrine product used was the standard concentration available at the institution (norepinephrine 16 mg diluted in 250 mL of dextrose 5% in water). If the maximum dose (15 mcg/min) or duration was reached, or if extravasation occurred, CVC placement was mandatory or at the clinician’s discretion. Extravasation antidotes (subcutaneous phentolamine and nitroglycerin paste, both to be administered at the site of extravasation) were readily available, and an order panel for peripheral norepinephrine with preselected dose ranges and antidotes was implemented in the electronic medical record system.

Duration

February 2019 to June 2021

Outcome Measures

Primary: number of days of central venous catheter (CVC) use that were avoided per patient

Secondary: safety outcomes included the incidence of extravasation events

Baseline Characteristics

  

All patients (N= 635)

 

  

Age, years (IQR)

 63 (55 to 71)    

Weight, kg (IQR)

 82.7 (68.9 to 99.3)    

Body mass index, kg/m2 (IQR)

 28.2 (23.7 to 33.6)    

Maximum dose, mcg/min (IQR)

 10 (6 to 15)    

Infusion duration, hours (IQR)

 5.8 (2.0 to 19.7)    

Required CVC

 292/603 (48.4%)    

Extravasation events

 35 (5.5%)    

Highest infiltration grade*

0

1

2

3

4

 

5 (14.3%)

16 (45.7%)

13 (37.1%)

0

1 (2.9%)**

    

Protocol criteria met at time of norepinephrine initiation

Catheter size criteria

Catheter placement location criteria

Catheter ultrasound confirmation criteria

Appropriate norepinephrine dose

 

529 (83.3%)

422 (66.5%)

316 (49.8%)

535 (84.3%)

    

Abbreviations: CVC= central venous catheter; IQR= interquartile range

* Infiltration grades: grade 0, no symptoms; grade 1, edema < 1 inch, cool to touch, with or without pain; grade 2, skin blanched, translucent, edema 1-6 inches in any direction, cool to touch, with or without pain; grade 3, skin blanched, translucent, gross edema > 6 inches, mild to moderate pain, possible numbness; grade 4, skin blanched, translucent, gross edema > 6 inches, deep pitting edema, circulatory impairment, moderate to severe pain

** One patient was graded as showing infiltration grade 4, but was transitioned to comfort care measures and died before being evaluated by the study team

Results

Endpoint

≤24 hours (n= 508)

>24 hours (n= 127)

Effect estimate (95% CI)

Infusion duration, hours (IQR)

3.8 (1.5 to 9.7)

 42.4 (32.4 to 66.1) --

Maximum dose, mcg/min (IQR)

 10 (5 to 15) 10 (7 to 15) -1.2 (-2.9 to 0.6)a

Extravasation events

 24 (4.7%) 11 (8.7%) 3.9 (-0.4% to 10.3%)b

Extravasation incidence, per 1,000 d of PIVC administration

 176.4 (113.1 to 262.5) 33.8 (16.9 to 60.4) 0.19 (0.09 to 0.39)c

Highest infiltration grade*

0

1

2

3

4

 

5 (20.8%)

10 (41.7%)

8 (33.3%) 

0

1 (4.2%)

 

0

6 (54.5%) 

5 (45.5%) 

0

0

8.0 (-23.3% to 39.1%)** 

Abbreviations: CI= confidence interval; MD= mean difference

* Evaluated only in the 35 patients experiencing an extravasation event (n= 24 and n= 11, respectively).

** Absolute percentage difference for highest infiltration grade ≥2.

a Mean difference

b Absolute percentage difference

c Incidence rate ratio

The study observed a median of 1 day (IQR 0-2 days per patient) of CVC use avoided per patient, with 51.6% of patients avoiding CVC placement for norepinephrine administration. Although 5.5% of patients experienced norepinephrine extravasation events (incidence of 75.8 events/1,000 days of PIVC administration; 95% CI 52.8-105.4 events/1,000 days), the resulting tissue injury was minimal.

Additionally, patients experiencing extravasation seemed to be older (MD 4.0 years; 95% CI -0.5 to 8.0 years) and to have undergone a longer duration of peripheral norepinephrine administration (MD 6.8 h; 95% CI -3.1 to 19.3 h). Notably, overall protocol adherence and adherence to individual protocol elements were not lower in patients experiencing extravasation.

Adverse Events

See results

Study Author Conclusions

This study suggests that implementing a protocol for peripheral administration of norepinephrine safely can avoid 1 CVC day in the average patient, with 51.6% of patients not requiring CVC insertion. No patient experienced significant ischemic tissue injury with the protocol used. These data support performance of a randomized, prospective, multicenter study to characterize the net benefits of peripheral norepinephrine administration compared with norepinephrine administration through a CVC.

InpharmD Researcher Critique

This was a prospective observational trial conducted at a single site, which limits the generalizability of the results. Additionally, without a comparator group, the benefits and risks of administering norepinephrine via PIVC versus CVC remain unclear. Moreover, since the protocol was not mandatory for all patients, selection bias may have led to a lower incidence of complications than if it had been required. Finally, given that the study reflects real-world experience with evolving protocols, it is uncertain whether the same results would be achieved with any specific protocol version.
 
References:

Yerke JR, Mireles-Cabodevila E, Chen AY, et al. Peripheral administration of norepinephrine. CHEST. 2024;165(2):348-355. doi:10.1016/j.chest.2023.08.019