What is the optimal approach to infiltration and extravasation of nonchemotherapy medications?
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* Abby Tarpey
* Shraddha Narechania
* Mark Malesker

The immediate response to leakage of intravenous (IV) medications is warm or cold compression and assessment of severity. If the severity is grade 3 or above,1 an antidote is needed and must be identified quickly. The antidote depends on the type of medication that has leaked.

In general, hyaluronidase is the antidote of choice for nonvesicant agents, but other agents include topical nitroglycerin, phentolamine, terbutaline, and sodium thiosulfate. These agents work by vasodilating to clear the drug from the area and neutralizing the harmful irritants.

## IMPORTANT DISTINCTIONS: TERMINOLOGY

An review of terminology is helpful when discussing leakage of IV fluids.

**A vesicant** is an agent capable of causing tissue damage when escaped from the intended vascular pathway into surrounding tissue.

**An irritant or nonvesicant** is an agent that causes discomfort including, aching, tightness, and phlebitis with or without inflammation, but does not typically cause tissue necrosis.

**Infiltration** is leakage of a nonvesicant solution into the surrounding tissue. It is a relatively common occurrence and can cause redness, swelling, and pain or discomfort but does not cause tissue necrosis.

**Extravasation** is leakage of vesicant fluid out of a blood vessel into surrounding tissue. It can cause more damage than infiltration of nonvesicant solutions and can lead to blistering, tissue ischemia, and necrosis. In extreme cases, surgical debridement, skin-grafting, or even amputation may be required.

In this article, we will use the terms extravasation and extravasated for any IV infusion-related leakage.

## THE PROBLEM

The frequency of extravasation in adults is between 0.1% and 6%.2 Some suggest the incidence is decreasing thanks to improved infusion procedure, early recognition of drug leakage, and training.2

The consequences of fluid leakage from a vessel into surrounding tissue vary depending on the agent being dispensed. Awareness of these agents and their potential consequences will enhance the likelihood of prompt recognition and treatment.

## IMMEDIATE INTERVENTIONS

The following immediate interventions are recommended to prevent complications: 

*   Stop administration of fluid

*   Disconnect the IV tubing, but leave the catheter or needle in place to facilitate aspiration of fluid from the extravasation site and, if indicated, administration of an antidote

*   Do not flush the line

*   Remove the catheter or needle if an antidote will not be administered into the extravasation site

*   If an antidote is indicated, inject it through the catheter to ensure delivery to the extravasation site, then remove the catheter

*   Elevate the site and apply warm or cold compresses.

### Thermal compression and massage

Thermal compression improves patient outcomes.3 Cooling with ice packs aids in vasocontriction, theoretically restricts spread of the drug, and decreases pain and inflammation in the area. Warming the affected area with dry heat promotes vasodilation and increases blood flow, enhancing dispersion of the vesicant agent and decreasing accumulation of the drug in the localized tissue.

The standard of care and recommended application schedule for both warming and cooling is 15 to 20 minutes 4 times daily for 24 to 48 hours.2 Some guidelines suggest up to 6 times daily for 1 or more days.2

Physical massage may aid in the dispersal of extravasated drugs. To monitor and document the leakage, a surgical felt pen is used to gently draw an outline on the skin of the affected area.

## GAUGING THE SEVERITY, SELECTING AN ANTIDOTE

Many patients with extravasation experience erythema, edema, ulceration, stinging, burning, pain, tissue-sloughing, and even necrosis. A severity of grade 3 or greater, which requires an antidote, is characterized by pain, swelling, sluggish capillary refill time, normal or decreased perfusion, and other symptoms (Table 1).1,4–6

View this table:
[TABLE 1](http://www.ccjm.org/content/90/5/292/T1)

TABLE 1 
Grading the severity of extravasation damage

Treatment differs depending on the extravasated medication, and the selection process may be complex. In general, hyaluronidase is the antidote of choice for nonvesicant agents. Other antidotes include topical nitroglycerin, phentolamine, terbutaline, and sodium thiosulfate. Their vasodilating effects clear the drug from the affected area and neutralize harmful irritants that cause discomfort (aching, tightness, and phlebitis with or without inflammation) but typically not tissue necrosis. The treatment varies depending on the medication involved and the grade of severity (Tables 2 and 3).1–8

View this table:
[TABLE 2](http://www.ccjm.org/content/90/5/292/T2)

TABLE 2 
Current antidotes for intravenous extravasation

View this table:
[TABLE 3](http://www.ccjm.org/content/90/5/292/T3)

TABLE 3 
Antidotes for nonchemotherapy drug extravasation

## CONTRAST MEDIA EXTRAVASATION

Extravasation of IV-administered iodine-based and gadolinium-based contrast media can cause serious tissue damage, including necrosis. While the incidence of contrast media extravasation is relatively low (between 0.1% and 0.9%),9–11 factors associated with increased risk of contrast extravasation include use of iodine-based contrast (as opposed to gadolinium contrast), use of automatic power injectors, high injection rates, patient-related factors (older age, female sex, cachexia, IV drug use, inpatient status), venous access site (dorsum of hand), and small-gauge needles (less than 22-gauge).9,12 Use of high-osmolar and high-viscosity contrast media increases the risk of extravasation. Prewarming the contrast agent to 37°C (98.6°F) lowers the viscosity and, in turn, the probability of extravasation.9

The clinical presentation of contrast extravasation resembles that of other vesicant drug extravasations and can include local pain, tenderness, swelling, redness, itching, and skin tightness. In more severe cases or with large-volume, high-osmolarity contrast extravasation, skin-blistering, soft-tissue necrosis, or compartment syndrome can occur.

Treatment requires immediate discontinuation of the infusion, aspiration of contrast if possible, conservative measures such as limb elevation and cooling compresses, and injection of hyaluronic acid. There is no set threshold of extravasate volume at which surgical consultation is warranted. However, it has been suggested that plastic surgery consultation be requested when extravasation volume is greater than 100 to 150 mL.9,13 Severe symptoms such as ulceration or necrosis may warrant surgical consultation regardless of extravasate volume.

## PREVENTION

Focusing on preventive measures will lower the risk of extravasation, promote patient trust, and increase patient satisfaction.2 Patient engagement is key to prevention. When infusing a vesicant, counsel the patient to immediately report changes in skin color, integrity or firmness, temperature, mobility, sensation, or pain.2 The vein used for infusion should be a large, intact vessel with good blood flow, specifically a basilic, cephalic, or antebrachial vein. Avoid veins in the hands, dorsum of the foot, any joint space, or antecubital fossa area.2 Always check for blood back-flow to ensure correct catheter positioning.2 When possible, use of a central venous catheter helps limit drug extravasation.14

## DISCLOSURES

The authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.

*   Copyright © 2023 The Cleveland Clinic Foundation. All Rights Reserved.

## REFERENCES

1.  The Royal Children’s Hospital Melbourne. Clinical guidelines (nursing). Extravasation injury management. [https://www.rch.org.au/rchcpg/hospital\_clinical\_guideline\_index/Extravasation\_Injury\_Management/](https://www.rch.org.au/rchcpg/hospital\_clinical\_guideline_index/Extravasation_Injury_Management/). Accessed April 11, 2023.
    
    

2.  Kim JT, Park JY, Lee HJ, Cheon YJ. Guidelines for the management of extravasation. J Educ Eval Health Prof 2020; 17:21. doi:10.3352/jeehp.2020.17.21
    
    [CrossRef](http://www.ccjm.org/lookup/external-ref?access_num=10.3352/jeehp.2020.17.21&link_type=DOI) 

3.  Roca-Sarsanedas J, Galimany-Masclans J, Regidor-Braojos AM, Falcó-Pegueroles A. Topical treatment of tissue damage due to extravasation of iodinated contrast using thermal compresses. J Tissue Viability 2022; 31(1):135–141. doi:10.1016/j.jtv.2021.12.0063.
    
    [CrossRef](http://www.ccjm.org/lookup/external-ref?access_num=10.1016/j.jtv.2021.12.0063&link_type=DOI) 

4.  Ong J, Van Gerpen R. Recommendations for management of non-cytotoxic vesicant extravasations. J Infus Nurs 2020; 43(6):319–343. doi:10.1097/NAN.0000000000000392
    
    [CrossRef](http://www.ccjm.org/lookup/external-ref?access_num=10.1097/NAN.0000000000000392&link_type=DOI) 
    
    [PubMed](http://www.ccjm.org/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fccjom%2F90%2F5%2F292.atom) 

5.  University of Illinois, Chicago. What are current recommendations for treatment of drug extravasation? [https://dig.pharmacy.uic.edu/faqs/2021-2/february-2021-faqs/what-are-current-recommendations-for-treatment-of-drug-extravasation](https://dig.pharmacy.uic.edu/faqs/2021-2/february-2021-faqs/what-are-current-recommendations-for-treatment-of-drug-extravasation). Accessed April 11, 2023.
    
    

6.  Reynolds PM, MacLaren R, Mueller SW, Fish DN, Kiser TH. Management of extravasation injuries: a focused evaluation of noncytotoxic medications. Pharmacotherapy 2014; 34(6):617–632. doi:10.1002/phar.1396
    
    [CrossRef](http://www.ccjm.org/lookup/external-ref?access_num=10.1002/phar.1396&link_type=DOI) 
    
    [PubMed](http://www.ccjm.org/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fccjom%2F90%2F5%2F292.atom) 

7.  Lau BC, Lee NH. Acyclovir extravasation: case report and review of the literature. Austin J Orthopade & Rheumatol 2016; 3(1):1026. [https://austinpublishinggroup.com/orthopedics-rheumatology/fulltext/ajor-v3-id1026.php](https://austinpublishinggroup.com/orthopedics-rheumatology/fulltext/ajor-v3-id1026.php). Accessed April 11, 2023.
    
    

8.  Fox AN, Villanueva R, Miller JL. Management of amiodarone extravasation with intradermal hyaluronidase. Am J Health Syst Pharm 2017; 74(19):1545–1548. doi:10.2146/ajhp160737
    
    [Abstract/FREE Full Text](http://www.ccjm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiYWpocCI7czo1OiJyZXNpZCI7czoxMDoiNzQvMTkvMTU0NSI7czo0OiJhdG9tIjtzOjIwOiIvY2Nqb20vOTAvNS8yOTIuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

9.  Roditi G, Khan N, van der Molen AJ, et al. Intravenous contrast medium extravasation: systematic review and updated ESUR Contrast Media Safety Committee guidelines. Eur Radiol 2022; 32(5): 3056–3066. doi:10.1007/s00330-021-08433-4
    
    [CrossRef](http://www.ccjm.org/lookup/external-ref?access_num=10.1007/s00330-021-08433-4&link_type=DOI) 

10. Nicola R, Shaqdan KW, Aran S, Prabhakar AM, Singh AK, Abujudeh HH. Contrast media extravasation of computed tomography and magnetic resonance imaging: management guidelines for the radiologist. Curr Probl Diagn Radiol 2016; 45(3):161–164. doi:10.1067/j.cpradiol.2015.08.004
    
    [CrossRef](http://www.ccjm.org/lookup/external-ref?access_num=10.1067/j.cpradiol.2015.08.004&link_type=DOI) 

11. Hwang EJ, Shin CI, Choi YH, Park CM. Frequency, outcome, and risk factors of contrast media extravasation in 142,651 intravenous contrast-enhanced CT scans. Eur Radiol 2018; 28(12):5368–5375. doi:10.1007/s00330-018-5507-y
    
    [CrossRef](http://www.ccjm.org/lookup/external-ref?access_num=10.1007/s00330-018-5507-y&link_type=DOI) 

12. Heshmatzadeh Behzadi A, Farooq Z, Newhouse JH, Prince MR. MRI and CT contrast media extravasation: a systematic review. Medicine (Baltimore) 2018; 97(9):e0055. doi:10.1097/MD.0000000000010055
    
    [CrossRef](http://www.ccjm.org/lookup/external-ref?access_num=10.1097/MD.0000000000010055&link_type=DOI) 

13. Wang CL, Cohan RH, Ellis JH, Adusumilli S, Dunnick NR. Frequency, management, and outcome of extravasation of nonionic iodinated contrast medium in 69,657 intravenous injections [published correction appears in Radiology 2015; 274(1):307]. Radiology 2007; 243(1):80–87. doi:10.1148/radiol.2431060554
    
    [CrossRef](http://www.ccjm.org/lookup/external-ref?access_num=10.1148/radiol.2431060554&link_type=DOI) 
    
    [PubMed](http://www.ccjm.org/lookup/external-ref?access_num=17392249&link_type=MED&atom=%2Fccjom%2F90%2F5%2F292.atom) 

14. 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. J Crit Care 2015; 30(3):653.e9–653.e6.53E17. doi:10.1016/j.jcrc.2015.01.014653.e6.53E17
    
    [CrossRef](http://www.ccjm.org/lookup/external-ref?access_num=653.e6.53E17&link_type=DOI)