Infiltration and Extravasation

Standards of Practice for Prevention, Recognition, and Management

Definitions

Infiltration refers to the inadvertent leakage of non-vesicant solution or medication from a vascular access device (VAD) into the surrounding tissue. Extravasation specifically describes the escape of vesicant agents—solutions or medications capable of causing tissue injury, necrosis, or blistering—into the perivascular space.

1.2 Core Standards

Three fundamental standards govern clinical practice in this area. First, organizations must reduce infiltration and extravasation risk through careful selection of appropriate VADs and insertion sites, combined with validation of device position and patency before and during infusion therapy. Second, clinical staff must regularly assess both peripheral and central vascular access device sites for signs and symptoms of infiltration and extravasation before and during each infusion. Third, appropriate interventions must be implemented immediately upon recognition of infiltration or extravasation, with the intervention matched to the characteristics of the solution or medication escaping from the vein.

Prevention Through Optimal Device Selection

2.1 Vascular Access Device Selection and Site Planning

Selecting the most appropriate VAD and insertion site represents the primary strategy for reducing infiltration and extravasation risk. Patients presenting with difficult venous access risk factors should be escalated to vascular access specialists or infusion teams as early as possible in their care trajectory (Ehmke, 2021; Massand et al., 2019; Marsh et al., 2020; Kim et al., 2020; Gong et al., 2021).

Research consistently demonstrates significant educational needs among nursing staff regarding risk factors, optimal VAD selection, recognition of complications, and treatment strategies for infiltration and extravasation across all healthcare settings and patient populations (Ehmke, 2021; Gong et al., 2021; Melo et al., 2020; Chan et al., 2020; Indarwati et al., 2020; Sisan et al., 2018; Özalp Gerçeker et al., 2018). A controlled before-and-after study in a neonatal unit demonstrated that implementing clinical practice guidelines for peripheral intravenous catheter insertion and management significantly reduced extravasation events (Chan et al., 2020).

2.2 Understanding Vesicant, Irritant, and Non-Vesicant Classifications

Clinical staff must recognize the critical differences between vesicant, non-vesicant, and irritant solutions and medications. Each organization should establish consensus on which medications are classified as vesicants and irritants based on their internal formularies and the specific patient populations they serve (Ehmke, 2021; Massand et al., 2019; Kim et al., 2020; Manrique-Rodríguez et al., 2021; David et al., 2020; Giménez Poderós et al., 2022; Ong & Van Gerpen, 2020; Vokurka et al., 2020).

The vesicant nature of certain antineoplastic and non-antineoplastic medications must be identified prior to administration. Clinical teams should be prepared to utilize recommended pharmacologic and non-pharmacologic treatments in the event of extravasation, or to escalate care to clinicians capable of managing these injuries (Ehmke, 2021; Gong et al., 2021; Melo et al., 2020; Chan et al., 2020; Roditi et al., 2022; Karius & Colvin, 2021; Vokurka et al., 2020; Hackenberg et al., 2021; Milcheski et al., 2018; Kimmel et al., 2018).

Current literature reveals a paucity of data on extravasation incidence and treatment recommendations, with many guidelines based on animal studies and case reports. This area requires further study, and there are recommendations to establish extravasation registries to improve dissemination of outcomes data (Özalp Gerçeker et al., 2018; Hackenberg et al., 2021; Kimmel et al., 2018; Corbett et al., 2019; van der Pol et al., 2017; ACR Committee on Drugs and Contrast Media, 2023; Dufficy et al., 2022).

Risk Factor Assessment

3.1 Framework for Risk Evaluation

Comprehensive evaluation of risk factors associated with infiltration and extravasation enables clinicians to determine appropriate monitoring frequency and evaluate alternative vascular access options for patients at increased risk, including consideration of central vascular access devices (Ehmke, 2021; Gong et al., 2021; Melo et al., 2020; Chan et al., 2020; Indarwati et al., 2020; Karius & Colvin, 2021; Kleidon et al., 2019; Özalp Gerçeker et al., 2018).

3.2 Patient-Specific Risk Factors

Multiple studies have identified patient-specific factors associated with increased risk of infiltration and extravasation (Ehmke, 2021; Kim et al., 2020; Gong et al., 2021; Roditi et al., 2022; Kleidon et al., 2019; Boyar & Galiczewski, 2021; Vokurka et al., 2020; Milcheski et al., 2018; Oncology Nursing Society, 2023; Boyar & Galiczewski, 2018; Loubani & Green, 2015; Wasserman et al., 2019; Chong et al., 2021; Hwang et al., 2018):

Sex and infection status play a role, with female patients and those with current infections demonstrating increased susceptibility. Sensory and communication factors create additional risk; patients with altered sensation near the VAD site due to neuropathy or application of pre-insertion pain relief products may not detect early warning signs, as may those who have difficulty communicating the onset of pain, tightness, or other discomfort.

Cognitive factors compound these risks. Patients with altered mental status or cognition—whether from encephalopathy, confusion, or sedating medications—cannot reliably report symptoms. Underlying disease processes that produce changes in vasculature or impaired circulation significantly increase vulnerability. These include malignancy, diabetes mellitus, lymphedema, systemic lupus erythematosus, Raynaud’s disease, peripheral neuropathy, and peripheral vascular disease. Venous access history matters as well; patients with difficulty establishing peripheral venous access related to history of multiple venipunctures or obesity present elevated risk.

Age-related factors deserve particular attention at both ends of the lifespan. Neonates and young children face increased risk due to their inability to communicate discomfort, fragile vasculature and skin, limited physiologic resources to repair cellular damage, and a lack of safe and effective VAD securement and dressing options appropriately sized for their anatomy (Gong et al., 2021; Indarwati et al., 2020; Karaoğlan et al., 2022; Kleidon et al., 2019; Özalp Gerçeker et al., 2018; Boyar & Galiczewski, 2021; Hackenberg et al., 2021; Dufficy et al., 2022; Fonzo-Christe et al., 2018). Elderly patients experience anatomical changes including loss of thickness of the dermal skin layer, thickening of the tunica intima and media, and loss of connective tissue that contribute to vein fragility and create challenges in vascular access.

3.3 Mechanical Risk Factors

Mechanical causes of infiltration and extravasation require assessment and preventive action. Reduction or loss of patency of the VAD or vessel may result from abnormalities such as fibrin sleeve formation, venous thrombosis, pinch-off syndrome, and catheter fracture (Ehmke, 2021; Melo et al., 2020; Chan et al., 2020; Taibi et al., 2020).

Patient movement and positioning affect VAD performance in multiple ways. Normal body movements, unpredictable patient activity (particularly in infants, children, and confused patients), events that increase tension on or malposition of the VAD (such as patient repositioning or transport), and procedures requiring specific positions (such as a “tucked arm” during surgery) all contribute to risk (Kleidon et al., 2019; Pysyk et al., 2019; Sampson, 2019).

Events that increase the risk of vessel trauma include rapid infusions and use of bolus features on infusion pumps (Marsh et al., 2020; Kim et al., 2020; Melo et al., 2020; ACR Committee on Drugs and Contrast Media, 2023; Abe-Doi et al., 2019). Insertion of the VAD in an area of flexion creates additional vulnerability (Gong et al., 2021). Notably, infiltration and extravasation rates are significantly higher in peripheral intravenous catheters inserted in the emergency department compared to other units, likely due to high-volume infusions, frequent insertion at the antecubital fossa, use of large-bore catheters, and blood sampling through the device (Marsh et al., 2020).

Multiple insertion attempts, especially in the same anatomic location, increase infiltration risk (Ehmke, 2021; Kim et al., 2020; Kleidon et al., 2019; Braga et al., 2018; Liew et al., 2021; Larsen et al., 2021). Catheter malposition occurring during the lifespan of the VAD presents ongoing concerns.

3.4 Reducing VAD Malposition Risk

Clinicians should take specific steps to reduce VAD malposition during insertion and throughout post-insertion care. For intraosseous devices, adequate needle length for the patient must be ensured per manufacturers’ recommendations (Wasserman et al., 2019; Sampson, 2019). For peripheral intravenous catheters, adequate vein purchase—meaning sufficient length of the catheter residing within the vessel—should be confirmed (Tran et al., 2020; Fonzo-Christe et al., 2018; Favot et al., 2019).

Central vascular access devices require particular vigilance. Extravascular CVAD tip malposition, dislodgement, or fracture can occur in many anatomical locations and at any point during dwell time. Clinicians should measure vessel depth in tissue using ultrasound prior to CVAD insertion to ensure all lumen exit sites are within the patient’s vasculature, since partial dislodgement can result in more proximal lumen exit sites infusing into subcutaneous tissue (Govil et al., 2019; Spencer, 2019).

Daily catheter position monitoring should be performed in inpatient settings, comparing measurements to those documented at insertion. In outpatient settings, regular monitoring should occur at appropriate intervals. All catheter lumens should be checked for blood return and flushed prior to use. Clinicians should not assume appropriate intravascular tip position of all lumens when blood aspirate is possible from one lumen but not all (Govil et al., 2019; Spencer, 2019).

In addition to mechanical risk factors, CVADs may gradually become malpositioned due to growth of the infant or child with a long-term device in place (Yu et al., 2020). Clinicians should monitor for sudden changes in clinical condition in patients of all ages that may indicate extravascular administration of medication involving a centrally administered vesicant. Warning signs include new onset hypoxia, respiratory distress, hypotension, abdominal distension or pain, edema, and airway impingement (Chan et al., 2020; Vokurka et al., 2020; Hackenberg et al., 2021; Yu et al., 2020; Cahill et al., 2021; Hong et al., 2022; Edison et al., 2021; Chen et al., 2020).

When evaluating new pleural effusion, abscess, or lesion in an area related to the CVAD, clinical criteria including radiologic imaging, laboratory values, and aspiration of fluid should be used to determine the presence of infiltration or extravasation versus other clinical complications. Administration of a vesicant (such as hypertonic parenteral nutrition in fragile vessels) and the mechanical forces of the catheter may cause vessel erosion, allowing the vesicant to invade surrounding structures including the liver, mediastinum, abdomen, and thoracic cavity (Spencer, 2019; Cahill et al., 2021; Hong et al., 2022).

Neonates face particularly high risk for extravasation with CVAD insertion, whether umbilical, peripherally inserted central catheter (PICC), or femoral catheter. Complications resulting in morbidity and mortality include ascites, abdominal compartment syndrome, hepatic laceration, hepatic necrosis, hepatic abscess, pleural effusion, pericardial effusion, and hemi-diaphragmatic paralysis (Yu et al., 2020; Chen et al., 2020; Baldo et al., 2022; Huang et al., 2021; Hargitai et al., 2019; Gupta et al., 2018; Ng et al., 2021; Rajendran & Sinha, 2021; Kotinatot et al., 2019; Kamupira et al., 2022; Yew et al., 2022).

Radiographic tests should be anticipated to validate CVAD tip location. Timing of CVAD removal depends on the plan of care based on identified extravascular location of the catheter tip. Assessment of the location of a subcutaneous tunnel or port pocket and its proximity to any wound helps determine if the long-term CVAD should be removed for healing to occur. Consultation with a wound care specialist should be considered.

3.5 Peripheral Intravenous Catheter-Specific Risk Factors

Several factors specific to peripheral intravenous catheters may increase infiltration and extravasation risk (Massand et al., 2019; Marsh et al., 2020; Melo et al., 2020; Roditi et al., 2022; Seo et al., 2020; Boyar & Galiczewski, 2021; Vokurka et al., 2020; Oncology Nursing Society, 2023; Milcheski et al., 2018; Corbett et al., 2019; Hwang et al., 2018; Fonzo-Christe et al., 2018; Braga et al., 2018):

PIVC sites in the hand, wrist, foot, ankle, antecubital fossa, and areas with minimal subcutaneous tissue coverage present elevated risk. When insertion in an area of flexion is deemed necessary, more frequent monitoring is required, joint stabilization may be needed, and consideration should be given to early removal and reinsertion in a location with reduced risk of complication.

Additional PIVC-specific risk factors include use of steel “butterfly” needles, inadequate catheter securement, short PIVCs with dwell time longer than 24 hours, and increased manipulation of the PIVC at the catheter hub. Inability to establish patency through positive blood return or site assessment during flushing (such as when diffuse edema is present), delivery of a vesicant in an insertion site below a recent venipuncture (less than 24 hours prior), and depth of the PIVC (which may delay visual signs and symptoms of failure when the tip lies in a deep vein, particularly in non-verbal patients) all contribute to risk. PIVC administration of contrast media also increases vulnerability.

3.6 Pharmacologic and Physiochemical Risk Factors

The pharmacologic or physiochemical properties of infusates significantly influence infiltration and extravasation risk and severity of tissue damage. Contributing factors include length of infusion of vesicant via a PIVC, drug concentration, volume escaping into the tissue, ability of surrounding tissues to absorb the drug, hyperosmolarity, non-physiological pH, the medication’s ability to bind DNA, the medication’s capacity to kill replicating cells or cause vascular constriction, and excipients such as alcohol or polyethylene glycol used in drug formulation (Ehmke, 2021; Gong et al., 2021; David et al., 2020; Melo et al., 2020; Roditi et al., 2022; Seo et al., 2020; Loubani & Green, 2015; Vokurka et al., 2020; Yew et al., 2022; Caballero Romero et al., 2018).

Early Recognition and Detection

4.1 Assessment Frequency and Visual Inspection

Limiting the extent of infiltration and extravasation injury requires both preventive measures and early recognition of signs and symptoms through regular visual inspection and bilateral palpation of limbs. VAD insertion sites should be assessed at a frequency based upon the specific patient population and characteristics of the infusion therapy (Ehmke, 2021; David et al., 2020; Melo et al., 2020; Chan et al., 2020; Roditi et al., 2022; Milcheski et al., 2018; Gil et al., 2017; Yew et al., 2022; Ray-Barruel et al., 2019; Richardson et al., 2021).

Establishing monitoring standards for VADs utilized in intraoperative and intraprocedural areas represents an area requiring further research, given inherent barriers to visualization including sterile drapes, tucked limbs, competing priorities, and rapid infusions (Fonzo-Christe et al., 2018; Mecoli et al., 2022; Park & Kim, 2020; Hoefnagel et al., 2021; Ang et al., 2022).

4.2 Recognizing Critical Complications

Acute abnormalities in pain, sensation, or circulation should be promptly recognized and reported. Compartment syndrome and arterial and nerve damage may result from infiltration or extravasation of sufficient infusate volume to cause tissue ischemia or injury. Significant long-term complications may include complex regional pain syndrome, neurovascular compromise, or limb amputation (Roditi et al., 2022; Milcheski et al., 2018; Corbett et al., 2019; ACR Committee on Drugs and Contrast Media, 2023; Wasserman et al., 2019; Park & Kim, 2020; Hoefnagel et al., 2021; Ang et al., 2022; Papatheodorou et al., 2022; Raveendran et al., 2019).

High risk for these complications exists with VAD insertion in small vessels, areas of flexion, or areas with tight subfascial compartments such as the hand, wrist, and forearm. If compartment syndrome is suspected, the affected extremity should be elevated to the level of the heart to optimize perfusion, and the surgeon or plastic surgeon should be notified immediately when circulatory or neurological compromise is suspected.

4.3 Signs and Symptoms

Observation of the VAD site and areas proximal and distal to the insertion site should assess for several abnormalities (Ehmke, 2021; Kim et al., 2020; Ong & Van Gerpen, 2020; Hackenberg et al., 2021; Wasserman et al., 2019; El-Zaatari et al., 2019):

Fluid leakage from the puncture site, subcutaneous tunnel, or port pocket may be visible or subcutaneous. Skin injury, including vesicle formation, may appear within hours (as with contrast media) or may be delayed for days (as with antineoplastic agents). Progression to ulceration may vary from a few days to one to two weeks, depending on the vesicant administered. Discoloration or hyperpigmentation may also be observed.

Other conditions with similar symptoms must be ruled out, including phlebitis, flare reactions, and rash (Kim et al., 2020; Ahn & Park, 2021). A notable case report illustrates subdural infiltration from a scalp PIVC in a neonate used to deliver fluid and blood products. The changes in neurovascular status were initially thought to represent intracranial hemorrhage but were found to result from significant intracranial infiltration (Fleiss et al., 2021).

4.4 Extremity Assessment

Assessment of the extremity and areas proximal and distal to the insertion site, with comparison to the contralateral limb, should include the following elements (Kim et al., 2020; David et al., 2020; Chan et al., 2020; Hackenberg et al., 2021; Govil et al., 2019):

Palpation of the insertion site assesses for swelling and pain. Swelling or edema may appear as a raised area under the skin near the peripheral VAD site or as an enlarged and tense extremity due to fluid accumulating in compartments of the extremity. Edema from a CVAD may appear as a raised area on the neck, chest, or groin. Circumference of both extremities should be compared if unilateral edema is noted, with comparison to baseline measurement at insertion when available. Changes in color may include redness or blanching; however, infiltration or extravasation into deep tissue may not produce visible color changes.

The patient’s report of pain should be elicited, with observation of non-verbal patients for other cues indicating pain. Pain may be the initial symptom and may be sudden and severe when associated with rapid injection of solution or medications. Pain may be out of proportion to the injury or may appear with passive stretching of the muscles in the extremity. Pain intensity may increase over time, which may indicate compartment syndrome (Kim et al., 2020; Gong et al., 2021; Melo et al., 2020; Santos et al., 2021; Hackenberg et al., 2021; ACR Committee on Drugs and Contrast Media, 2023).

4.5 Detection Technology

Infiltration and extravasation detection technology may aid in early recognition, though further research is needed to determine optimal use. Options under investigation include thermosensitive crystal film, near infrared camera, radiofrequency detection, gamma scintillation, color flow doppler, impulse oscillometry, and point-of-care ultrasound (van Rens et al., 2022; Roditi et al., 2022; Abe-Doi et al., 2019; Gautam et al., 2017; Frunza et al., 2022; Abe-Doi et al., 2020; Hinricher et al., 2021; Hirata et al., 2023; Abe-Doi et al., 2020).

Careful assessment in conjunction with detection technology remains essential, as devices may fail to detect abnormalities or fail to adequately warn clinicians, especially in settings where the VAD is not readily accessible (van Rens et al., 2022; Frunza et al., 2022). Critically, clinicians should not rely on alarms from electronic infusion pumps to identify infiltration and extravasation; alarms are not designed to detect the presence or absence of complications. Electronic infusion pumps do not cause infiltration or extravasation; however, they may mask or exacerbate the problem until the infusion is stopped (van Rens et al., 2022; Pysyk et al., 2019).

4.6 Contrast Media Administration

When contrast administration is planned, a VAD designed for contrast administration should be inserted in an optimal location to ensure adequate monitoring during the procedure. Proper function should be assessed prior to, during, and following contrast media infusion, and delivery of contrast should be adjusted to conform to the chosen VAD (Roditi et al., 2022; ACR Committee on Drugs and Contrast Media, 2023; Hwang et al., 2018; Stowell et al., 2020).

Extravasation can occur with both manual and automated delivery of contrast. Automated power or pressure injectors produce a jet of fluid exiting the catheter tip. Distal tip malposition has been documented following power injection in PICCs, and it has been postulated that this jet could induce vessel perforation and extravasation (Roditi et al., 2022; ACR Committee on Drugs and Contrast Media, 2023; Raveendran et al., 2019; Papatheodorou et al., 2022).

Fluid warming may be associated with lower rates of extravasation. Fluid with high viscosity, such as contrast media, requires less force to administer when warmed to 37°C (Roditi et al., 2022; ACR Committee on Drugs and Contrast Media, 2023; Hwang et al., 2018; Basharat et al., 2022). Use of extravasation detection accessories, such as equivalent dose rate monitoring, should be considered to provide early detection, automated interruption of power injection, and guidance for contrast extravasation management (Roditi et al., 2022; Mazzara et al., 2022; Tylski et al., 2021).

Immediate Response to Infiltration and Extravasation

5.1 Initial Actions

Upon identification of an infiltration or extravasation injury, the infusion must be stopped immediately and appropriate interventions initiated (Ehmke, 2021; Kim et al., 2020; Melo et al., 2020; Chan et al., 2020; Roditi et al., 2022; Ong & Van Gerpen, 2020; Vokurka et al., 2020; Stowell et al., 2020).

Do not flush the VAD, as this will inject additional medication into the tissue. The administration set should be disconnected from the catheter hub, and aspiration from the catheter or implanted port access needle attempted with a small syringe, even though a very small amount of fluid may be retrieved. The role of aspiration is not clear with extravasation of contrast media (Ehmke, 2021; Kim et al., 2020; Melo et al., 2020; Chan et al., 2020; Roditi et al., 2022; Ong & Van Gerpen, 2020; Vokurka et al., 2020; Hackenberg et al., 2021; Kimmel et al., 2018; Corbett et al., 2019; ACR Committee on Drugs and Contrast Media, 2023; Gil et al., 2017).

The peripheral catheter or implanted vascular access port access needle should be removed (Ehmke, 2021; Kim et al., 2020; Vokurka et al., 2020; Kimmel et al., 2018; Canadian Vascular Access Association, 2019; Lv et al., 2021). Application of pressure to the area should be avoided (Kim et al., 2020; Vokurka et al., 2020; Santos et al., 2021). The extremity should be elevated to encourage lymphatic reabsorption of the solution or medication, unless compartment syndrome is suspected (Massand et al., 2019; Melo et al., 2020; Roditi et al., 2022; Ong & Van Gerpen, 2020; Corbett et al., 2019; ACR Committee on Drugs and Contrast Media, 2023; Gil et al., 2017). The affected extremity should be avoided for subsequent VAD insertion until resolved (Canadian Vascular Access Association, 2019).

5.2 Site Assessment Following Identification

Thorough assessment of the insertion site and surrounding tissue should include assessment of the area distal to the VAD site for capillary refill, sensation, and motor function (Ong & Van Gerpen, 2020; Santos et al., 2021; ACR Committee on Drugs and Contrast Media, 2023; Wasserman et al., 2019). Using a skin marker, the area suspected of infiltration or extravasation should be outlined to assess progression (Melo et al., 2020; Roditi et al., 2022). The area should be photographed to identify progression or exacerbation of the tissue injury in accordance with organizational policy (Ehmke, 2021; Melo et al., 2020; Karius & Colvin, 2021).

The volume of solution that has escaped into the tissue should be estimated based on the original amount of solution in the container, the amount remaining when stopped, and rate and duration of injection or infusion (Vokurka et al., 2020; Gil et al., 2017; Raveendran et al., 2019). Estimated extravasated volumes of contrast media less than 50 mL are more likely to resolve with conservative treatment, while volumes greater than 50 mL are at higher risk to cause tissue damage requiring treatment. However, the patient’s symptoms should dictate treatment options over the estimated extravasated volume. Radiologic imaging to evaluate a contrast extravasation is rarely indicated (Roditi et al., 2022; ACR Committee on Drugs and Contrast Media, 2023; Hwang et al., 2018; Raveendran et al., 2019).

5.3 Provider Notification and Treatment Protocol Activation

The provider should be notified about the event and the established treatment protocol or prescribed treatment activated (Ehmke, 2021; Kim et al., 2020; Melo et al., 2020; Roditi et al., 2022; Vokurka et al., 2020; Milcheski et al., 2018; ACR Committee on Drugs and Contrast Media, 2023; Gil et al., 2017).

The need for surgical consultation is based on organizational policy, clinical signs and symptoms and their progression, volume of injury, and the tissue-destroying nature of a vesicant medication. Treatment options that may be considered include subcutaneous irrigation with or without hyaluronidase, open incision and irrigation, small incisions followed by massage to force drainage, and debridement with skin graft or flap as indicated. The paucity of evidence supporting one surgical intervention over another means consideration should be given to the risks and benefits of conservative versus invasive treatment (Massand et al., 2019; Hackenberg et al., 2021; Milcheski et al., 2018; Little et al., 2020).

Treatment Protocols

6.1 General Treatment Principles

Treatment should be initiated promptly as appropriate for the type and volume of solution or medication in the tissue surrounding the VAD, with the goal of limiting damage from medication or solution exposure. Organizations should provide convenient access to the list of vesicants and irritants, infiltration and extravasation management protocols, electronic order forms, supplies, and other materials needed to manage the event (Massand et al., 2019; Chan et al., 2020; Ong & Van Gerpen, 2020; Santos et al., 2021; Corbett et al., 2019; Gil et al., 2017).

Wet compresses should be avoided, as they may cause maceration (Vokurka et al., 2020; Santos et al., 2021).

6.2 Heat and Cold Application

High-quality evidence to recommend use of heat or cold application in the treatment of extravasation injury is lacking (Ong & Van Gerpen, 2020; Hackenberg et al., 2021; ACR Committee on Drugs and Contrast Media, 2023). The rationale for cold application is to decrease absorption, keep the infusate localized, and decrease inflammation, while heat is used to encourage vasodilation and improve blood flow to disperse the medication through the tissue (Ehmke, 2021; Kim et al., 2020; Santos et al., 2021).

Use of cold and heat applications are recommended in contrast extravasation, with a general preference for cold due to the potential to reduce inflammation (Roditi et al., 2022; ACR Committee on Drugs and Contrast Media, 2023). A scoping review on treatment of extravasation in infants and children found that cold and heat application is rarely used in this population (Corbett et al., 2018).

Dry, cold compresses should be applied for DNA-binding agents and valproate because the goal is to cause vasoconstriction to localize the medication in the tissue and reduce inflammation (Ehmke, 2021; Kim et al., 2020; Melo et al., 2020; Vokurka et al., 2020; Gil et al., 2017). Cold compresses should not be used with extravasation in the presence of agents that may cause vasoconstriction or in the presence of vaso-occlusive events such as sickle cell anemia (Ong & Van Gerpen, 2020; Santos et al., 2021). If dexrazoxane is indicated, the cold compress should be removed 15 minutes before the infusion of dexrazoxane begins (Ehmke, 2021; Melo et al., 2020; Vokurka et al., 2020; Kimmel et al., 2018).

Dry, warm compresses should be applied for non-DNA binding agents to encourage vasodilation (Ehmke, 2021; Kim et al., 2020; Gil et al., 2017).

6.3 Antidotes

Dexrazoxane

Daily intravenous infusion of dexrazoxane over 3 days is the recommended antidote for anthracycline extravasation, including liposomal and pegylated anthracycline formulations (Ehmke, 2021; Melo et al., 2020). The infusion should begin within 6 hours of the extravasation and be infused into the opposite extremity (Ehmke, 2021; Melo et al., 2020; Vokurka et al., 2020). Topical dimethyl sulfoxide (DMSO) should not be applied to patients receiving dexrazoxane, as it may diminish dexrazoxane efficacy (Melo et al., 2020; Vokurka et al., 2020).

Hyaluronidase

Hyaluronidase is not considered an antidote to a specific vesicant but rather an enzyme that increases absorption and dispersion of the medication or solution in the tissue. Its use is reported with cytotoxic and non-cytotoxic agents, including both acidic and alkalotic drugs (such as amiodarone and phenytoin), vinca alkaloids, as well as hyperosmolar solutions (such as parenteral nutrition) and calcium salts. Recombinant hyaluronidase is not derived from animals and may have a lower risk of allergic response. Subcutaneous injection within 1 hour of the extravasation event produces the best response. Use of dry heat in conjunction with hyaluronidase works synergistically to increase blood flow and disperse the extravasated drug. Hyaluronidase is not considered first-line treatment for contrast extravasation (Ehmke, 2021; Melo et al., 2020; Chan et al., 2020; Roditi et al., 2022; Ong & Van Gerpen, 2020; Vokurka et al., 2020; ACR Committee on Drugs and Contrast Media, 2023; Oncology Nursing Society, 2023; Corbett et al., 2018).

Subcutaneous saline irrigation or saline irrigation with prior hyaluronidase administration for vesicant removal and dispersion in neonates should be considered. Further study is needed in the use of this practice, as resolution with conservative treatment is common (van Rens et al., 2022; Yew et al., 2022; Corbett et al., 2018).

Sodium Thiosulfate

Sodium thiosulfate is recommended for mechlorethamine extravasation and has been suggested for bendamustine, calcium, and large extravasations of cisplatin (Ehmke, 2021; David et al., 2020; Melo et al., 2020; Corbett et al., 2018; Pacheco Compaña et al., 2018).

Phentolamine and Alternative Vasodilators

Phentolamine is preferred for vasopressor extravasation. Normal perfusion of the area may be seen within 10 minutes of administration. Repeated injection may be necessary if hypoperfusion is still present or if vasoconstriction is extending to a greater area (Ong & Van Gerpen, 2020; Santos et al., 2021; Gil et al., 2017).

Terbutaline injection has been used for vasopressor extravasation when phentolamine is not immediately available (David et al., 2020; Ong & Van Gerpen, 2020). Topical nitroglycerin 2% may be applied as a 1-inch strip to the site of vasopressor extravasation in the absence of phentolamine, repeated every 8 hours as clinically indicated (David et al., 2020; Ong & Van Gerpen, 2020; Shrestha et al., 2020).

Corticosteroids

Use of oral, topical, or intralesional steroid should be considered on a case-by-case basis. Single-center studies and case reports have reported reduced inflammation and swelling; however, evidence of benefit is inconsistent and may not be recommended (David et al., 2020; Melo et al., 2020; Roditi et al., 2022; Vokurka et al., 2020).

6.4 Irrigation and Washout Procedures

Irrigation or washout may assist in removal of specific infusates from surrounding tissue, including acidic agents, alkalotic agents, contrast media, specific cytotoxic agents, and parenteral nutrition (Melo et al., 2020; Roditi et al., 2022; Hackenberg et al., 2021; Corbett et al., 2019; Gil et al., 2017; Taibi et al., 2020; Van Look et al., 2022).

Other treatments reported in the treatment of severe tissue injury due to extravasation include negative pressure wound therapy, needle aspiration, emergency evacuation with low-pressure suction, ethacridine lactate dressing with phototherapy, acellular fish skin graft dressing, and dehydrated human amniotic membrane allograft (Massand et al., 2019; Milcheski et al., 2018; Boyar & Galiczewski, 2018; Ahn & Park, 2021; Van Look et al., 2022; Girard et al., 2019; Lu et al., 2021; Faraji et al., 2022).

Injection of an acidic or alkaline medication to neutralize the pH of an extravasated acidic or alkaline vesicant should be avoided, as the resulting chemical reaction could cause gas formation and exacerbate the tissue injury (David et al., 2020; Stefanos et al., 2023).

While skin discoloration from iron infiltration may be permanent, laser treatment has been reported to be successful in reducing staining (Eggenschwiler et al., 2020).

Documentation and Standardized Assessment

7.1 Standardized Assessment Tools

A standardized age- or population-specific tool or definition should be used to consistently evaluate infiltration and extravasation events from all types of VADs. The chosen tool should be valid, reliable, and clinically feasible. The selected scale should be accompanied by appropriate interventions to manage each level of injury on the scale. Several scales have been published; however, further research is needed to establish validity and interrater reliability for specific populations (Kim et al., 2020; Chan et al., 2020; Roditi et al., 2022; Özalp Gerçeker et al., 2018; Ong & Van Gerpen, 2020; Santos et al., 2021; Corbett et al., 2019; Dufficy et al., 2022; Yew et al., 2022).

An infant infiltration scale was recently revised and found to be valid and reliable for this population in an observational, prospective study (Incekar et al., 2019).

7.2 Documentation Requirements

A standardized format should be used to document initial and ongoing assessment and monitoring of the infiltration or extravasation site and all factors involved with the event (Melo et al., 2020; van Rens et al., 2022; Ong & Van Gerpen, 2020; Santos et al., 2021; Kimmel et al., 2018; ACR Committee on Drugs and Contrast Media, 2023; Gil et al., 2017; Fonzo-Christe et al., 2018).

Accuracy of PIVC complication rates (including phlebitis, extravasation, and occlusion) is reduced by clinical knowledge deficits in symptom recognition, gaps in documentation, and a lack of consistent PIVC outcome definitions used in the literature (Ehmke, 2021; Marsh et al., 2020; Gong et al., 2021; Indarwati et al., 2020; Sisan et al., 2018; Özalp Gerçeker et al., 2018; Atay et al., 2021).

Ongoing Monitoring and Follow-Up

Site monitoring should continue as needed based on severity of the event and the venue of care, as signs and symptoms of infiltration and extravasation may be delayed in presentation. Changes in the area should be assessed by measurement and photography, with observation of skin integrity, level of pain, sensation, and motor function of the extremity (David et al., 2020; Melo et al., 2020; Karius & Colvin, 2021; Özalp Gerçeker et al., 2018; Gil et al., 2017; Fonzo-Christe et al., 2018; Ahn & Park, 2021).

Inflammation following contrast media extravasation generally peaks at 24-48 hours from the event (ACR Committee on Drugs and Contrast Media, 2023). Conducting follow-up phone calls or a follow-up visit to evaluate progression of an extravasation in the outpatient setting should be considered (Roditi et al., 2022; Karius & Colvin, 2021; Santos et al., 2021; ACR Committee on Drugs and Contrast Media, 2023).

Patient and Caregiver Education

The patient and caregivers should be educated regarding extravasation risk to improve prompt recognition of symptoms (Ehmke, 2021; Kim et al., 2020; David et al., 2020; Melo et al., 2020; Chan et al., 2020; Roditi et al., 2022; Vokurka et al., 2020; Braga et al., 2018; ACR Committee on Drugs and Contrast Media, 2023; El-Zaatari et al., 2019).

Pre-infusion education should address the risks of receiving an infusion prior to administration, emphasizing the signs and symptoms to immediately report. Post-infusion education should cover the possible progression of signs and symptoms of infiltration or extravasation, the need to protect the site from sunlight, and the frequency of follow-up visits to the provider as needed.

Quality Improvement

Infiltration and extravasation incidents causing harm or injury should be reviewed using adverse event reports and health record reviews for quality improvement opportunities (Ehmke, 2021; Melo et al., 2020; Karius & Colvin, 2021; Milcheski et al., 2018; Mecoli et al., 2022; Little et al., 2020).

Organizations should consider performing an investigation of each significant extravasation event (such as root cause analysis) to identify and implement needed quality improvement strategies.

Appendix A: Quick Reference Tables

A.1 Patient Risk Factor Summary

A.2 Mechanical Risk Factors

A.3 Antidote Quick Reference

A.4 Immediate Response Checklist

1. Stop infusion immediately
2. Do NOT flush VAD
3. Disconnect administration set
4. Attempt aspiration with small syringe
5. Remove peripheral catheter or port access needle
6. Avoid pressure to area
7. Elevate extremity (unless compartment syndrome suspected)
8. Assess distal capillary refill, sensation, motor function
9. Outline area with skin marker
10. Photograph per organizational policy
11. Estimate extravasated volume
12. Notify provider and activate treatment protocol
13. Avoid affected extremity for future VAD insertion until resolved

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Document Version: 1.0 Last Updated: January 2026 This document is intended as an educational resource for clinical professionals. Individual patient circumstances and institutional policies should guide clinical decision-making.