No products in the cart.
MODULE 13: IV BAG SAFETY & LINE MANAGEMENT
Section 5: Extravasation: Prevention and Antidotes
In this capstone section, we confront one of the most serious and visually dramatic complications of IV therapy: extravasation. This is the moment where your preventative expertise has been breached and you must transition into a role of rapid crisis management. You will learn to differentiate simple infiltration from true extravasation, master the classification of drugs as irritants versus vesicants, and understand the mechanisms by which they inflict catastrophic tissue damage. Most importantly, you will learn your critical, time-sensitive role in the immediate response, including the preparation and dispensing of the specific antidotes that can mitigate harm and preserve tissue.
5.1 From Leak to Lesion: Defining Infiltration vs. Extravasation
Understanding the critical distinction that dictates the emergency response.
While often used interchangeably in casual conversation, the terms infiltration and extravasation describe two distinct events with vastly different clinical consequences. As a pharmacist, your precise use of this language is critical for communicating the level of risk and the urgency of the required response. Both events begin the same way: the tip of an IV catheter slips out of the vein, and the fluid being infused begins to leak into the surrounding subcutaneous tissue. What happens next depends entirely on the chemical nature of the fluid that is leaking.
| Event | Definition | Signs & Symptoms | Consequence |
|---|---|---|---|
| Infiltration | The leakage of a non-vesicant solution or medication into the surrounding tissue. | Swelling/edema, skin that is cool to the touch and blanched (pale), tenderness or discomfort, sluggish or stopped infusion. | Generally causes temporary discomfort and swelling. The primary harm is the interruption of therapy. Tissue damage is rare unless very large volumes are involved. |
| Extravasation | The leakage of a vesicant solution or medication into the surrounding tissue. | Can include all the signs of infiltration, but often progresses to burning pain, blistering, skin discoloration (redness or purple), and eventually tissue necrosis (death) and sloughing. | A medical emergency that can lead to severe, long-term complications including full-thickness tissue loss, nerve damage, compartment syndrome, and the need for surgical debridement or amputation. |
Your role in prevention is to identify the drugs that have the potential to cause extravasation and ensure they are administered via the safest possible route (i.e., a central line). Your role in treatment is to recognize the event and immediately deploy the correct emergency protocol and antidote.
Retail Pharmacist Analogy: Spilling Water vs. Spilling Bleach
Imagine you are stocking shelves and accidentally knock over a bottle. If the bottle contains purified water, the result is a simple infiltration. You have a mess on the floor, you have to stop what you’re doing to clean it up, and the product is lost, but there is no real danger. You clean it up with paper towels and move on.
Now, imagine the bottle you knocked over was concentrated industrial bleach. The result is an extravasation. This is not just a mess; it’s a hazardous material spill. The bleach will immediately begin to damage the floor tiles, create noxious fumes, and pose a severe risk to anyone who touches it. You don’t just grab paper towels. You grab the official spill kit, don personal protective equipment (gloves, goggles), use a specific neutralizing agent, and follow a strict cleanup protocol to prevent further harm. The initial event—a spilled bottle—was the same, but the nature of the substance dictated a completely different, more urgent, and more specialized response.
5.2 The Spectrum of Harm: A Masterclass on Vesicants and Irritants
Classifying drugs based on their potential to cause tissue damage.
Not all drugs that are “bad” for peripheral lines are created equal. There is a spectrum of potential harm. As a pharmacist, you must understand this spectrum to properly risk-stratify medications and make appropriate recommendations for line selection and monitoring. The two major categories are irritants and vesicants.
5.2.1 Irritants: The Agents of Inflammation
An irritant is a drug that causes a local inflammatory reaction (phlebitis) at the infusion site, characterized by pain, redness, and swelling. However, they typically do not cause blistering or tissue necrosis. The inflammation will usually resolve on its own once the infusion is stopped and the catheter is removed. While uncomfortable for the patient and a cause for frequent IV line restarts, they do not usually cause long-term damage.
Mechanism: The inflammation is often caused by the drug’s non-physiologic pH or high osmolarity, which irritates the endothelial lining of the small peripheral vein.
Pharmacist’s Role: For irritants, your role is to mitigate the risk. This can involve recommending that the drug be further diluted, infused at a slower rate, or administered through a larger vein (like in the AC fossa) to maximize hemodilution. A short-term course may be tolerated peripherally, but for a longer course, you should advocate for a central line.
| Common Intravenous Irritants | ||
|---|---|---|
| Potassium Chloride (≤ 20 mEq/100mL) | Erythromycin | Nafcillin |
| Vancomycin (≤ 5 mg/mL) | Clindamycin | Cefepime |
| Dextrose (>10%) | Ciprofloxacin | Ganciclovir |
| Phenobarbital | Diazepam | Voriconazole |
5.2.2 Vesicants: The Agents of Necrosis
A vesicant is a drug that can cause severe, blistering tissue damage that can progress to full-thickness necrosis and sloughing. Extravasation of a vesicant is a medical emergency. These drugs should be administered through a central line whenever possible. If peripheral administration is absolutely unavoidable, it must be done with extreme caution, using a newly placed catheter in a large vein, with frequent site checks by the nurse.
Mechanism: Vesicants cause damage through a variety of direct cytotoxic mechanisms which we will explore in the next section.
Pharmacist’s Role: Your role is to act as the primary gatekeeper. You must identify these drugs and, in almost all cases, insist on central line placement before dispensing them. You are the expert who understands that the risk of peripheral administration is too great to accept.
| Common and High-Risk Intravenous Vesicants | ||
|---|---|---|
| Vasopressors | Chemotherapy Agents | Electrolytes & Other |
| Norepinephrine | Doxorubicin (Anthracycline) | Calcium Chloride |
| Epinephrine | Daunorubicin (Anthracycline) | Parenteral Nutrition (TPN) >900 mOsm/L |
| Dopamine | Vincristine (Vinca Alkaloid) | Hypertonic Saline (e.g., 3%) |
| Phenylephrine | Vinblastine (Vinca Alkaloid) | Potassium Chloride > 20 mEq/100mL |
| Vasopressin | Mechlorethamine | Promethazine |
| Paclitaxel | Phenytoin | |
| Vancomycin (> 5 mg/mL) | ||
5.3 Mechanisms of Tissue Damage: A Pharmacological Deep Dive
Understanding *how* vesicants destroy tissue to inform the treatment strategy.
Understanding the specific mechanism by which a vesicant causes harm is not just an academic exercise; it is crucial for determining the correct emergency response, particularly the choice of antidote and the use of thermal compresses. Vesicants can be broadly classified into two main categories based on their mechanism of cytotoxicity.
5.3.1 Category 1: DNA-Binding Vesicants
This category primarily includes many cytotoxic chemotherapy agents. Once these drugs extravasate, they are taken up by healthy cells in the subcutaneous tissue. They then bind to the DNA within the cell nucleus, causing irreversible cell death (apoptosis or necrosis). The most dangerous feature of this class is the phenomenon of “drug sequestration.” The dead cells lyse and release the drug, which is then taken up by adjacent healthy cells, creating a vicious, ever-expanding circle of tissue death. This is why an untreated anthracycline extravasation can continue to worsen for weeks or even months.
Examples: Anthracyclines (Doxorubicin, Daunorubicin, Idarubicin), Mechlorethamine.
Treatment Rationale: The goal is to either neutralize the drug in the tissue or to facilitate its systemic removal before it can cause more damage. For anthracyclines, the specific antidote dexrazoxane (Totect®) is used to chelate iron and prevent the formation of the free radicals that cause the DNA damage.
5.3.2 Category 2: Non-DNA-Binding Vesicants
This is a much broader category of drugs that cause tissue damage through a variety of other mechanisms. Unlike the DNA-binding agents, the damage is typically localized and self-limiting once the infusion is stopped. The drug does not get recycled to kill adjacent cells.
| Mechanism | Description | Example Drugs |
|---|---|---|
| Osmotic Damage | Extremely hyperosmolar solutions (>900 mOsmol/L) draw massive amounts of water out of the cells in the subcutaneous space, causing cellular dehydration, collapse, and an inflammatory response that leads to necrosis. | Parenteral Nutrition, Dextrose >20%, Hypertonic Saline, Concentrated Potassium Chloride. |
| pH Extremes | Solutions with a pH outside the physiologic range of 5-9 cause direct chemical burns to the tissue. Highly acidic solutions cause coagulation necrosis, while highly alkaline solutions cause liquefaction necrosis. | Acidic: Vancomycin, Vasopressors (Norepinephrine, Dopamine) Alkaline: Phenytoin, Acyclovir |
| Vasoconstriction | This is the primary mechanism for vasopressor extravasation. The potent alpha-1 adrenergic agonism of drugs like norepinephrine causes intense, localized vasoconstriction of the blood vessels in the subcutaneous tissue. This cuts off blood flow (ischemia) to the area, leading to tissue death. | Norepinephrine, Epinephrine, Dopamine, Phenylephrine. |
| Tubulin Disruption | Specific to Vinca Alkaloid chemotherapy agents. These drugs disrupt the cellular microtubules, which are essential for cell division and structure. This leads to cell death and a potent inflammatory response. | Vincristine, Vinblastine, Vinorelbine. |
Treatment Rationale: For these agents, the primary goal is to dilute and disperse the drug to minimize its local concentration. This is the rationale for using antidotes like hyaluronidase, which breaks down the extracellular matrix to allow the drug to spread out and be absorbed systemically.
5.4 The Extravasation Protocol: A Pharmacist-Led Crisis Response
Your step-by-step guide from the initial alert to antidote delivery.
When a nurse calls you to report a suspected extravasation, you become the medication crisis manager. Your calm, methodical response can be the difference between a minor injury and a catastrophic outcome. Every hospital has a formal extravasation policy, and you must know yours intimately. The following steps represent a best-practice, pharmacist-driven workflow.
5.4.1 The First 5 Minutes: The Immediate Bedside Response
The initial actions taken in the first few minutes are critical for limiting the extent of the damage. While the nurse is the one at the bedside, you must be able to coach them through these steps over the phone while you prepare the antidote.
- STOP the Infusion Immediately: This is the absolute first step to prevent any more drug from leaking into the tissue.
- DO NOT Remove the Catheter: Leave the IV catheter in place. It may be needed to aspirate fluid or administer the antidote.
- Disconnect and Aspirate: Disconnect the IV tubing from the catheter hub. Attach a small (3-5 mL) syringe to the hub and gently pull back to aspirate any residual drug and blood from the catheter and surrounding tissue.
- Elevate the Extremity: Raise the affected limb on pillows to help reduce swelling and encourage fluid resorption.
- Notify the Prescriber: The nurse must notify the physician or advanced practice provider immediately.
- APPLY Thermal Compress (Cold vs. Warm): This is a critical decision point that depends on the extravasated drug. Applying the wrong type of compress can worsen the injury.
Deep Dive: Cold vs. Warm Compresses—A Critical Decision
The choice of thermal compress is based on the vesicant’s mechanism of injury. Your ability to provide this guidance instantly is a key pharmacist competency.
| Compress Type | Rationale | When to Use (Key Examples) |
|---|---|---|
| Cold Compresses | Causes vasoconstriction, which helps to localize the extravasated drug and prevent it from spreading. It also reduces local inflammation and pain. This is the correct choice for MOST vesicants. | Anthracyclines (Doxorubicin), most other chemotherapies, hyperosmolar solutions. |
| Warm Compresses | Causes vasodilation, which helps to disperse the drug, increasing its systemic absorption and diluting its local concentration. This is only used for a specific few drug classes. Applying warm compresses to a DNA-binding agent would be catastrophic, as it would spread the drug to more healthy cells. | Vinca Alkaloids (Vincristine, Vinblastine) and Vasopressors (Norepinephrine, Dopamine) after phentolamine has been administered. |
5.4.2 The Extravasation Kit & Antidote Masterclass
While the nurse is performing the initial steps, you will proceed to the pharmacy’s dedicated, sealed extravasation kit. You will grab the kit and the specific antidote required and take them to the patient’s unit. Your role is to prepare the antidote with 100% accuracy under pressure.
Antidote #1: Hyaluronidase
Mechanism: An enzyme that temporarily breaks down hyaluronic acid in the subcutaneous tissue, increasing its permeability. This allows the extravasated drug to be dispersed over a larger area and absorbed systemically, reducing its local concentration and toxicity.
Indicated for: Vinca alkaloids (Vincristine), taxanes (Paclitaxel), hyperosmolar solutions (TPN, high-concentration electrolytes).
Preparation & Administration:
- Reconstitute the hyaluronidase vial (e.g., 150 units) with 1 mL of Normal Saline.
- Withdraw the entire 1 mL into a tuberculin syringe.
- The provider will administer it as five 0.2 mL subcutaneous injections into and around the periphery of the extravasation site.
- Change the needle before each new injection.
- After injections are complete, apply warm compresses to the area to enhance drug dispersal.
Antidote #2: Phentolamine
Mechanism: An alpha-1 adrenergic antagonist. It directly counteracts the intense vasoconstriction caused by extravasated vasopressors, restoring local blood flow (perfusion) to the ischemic tissue and preventing necrosis.
Indicated for: Vasopressors (Norepinephrine, Epinephrine, Dopamine, Phenylephrine).
Preparation & Administration:
- Dilute 5 to 10 mg of phentolamine in 10 mL of Normal Saline.
- The provider will use this solution to inject small amounts subcutaneously, infiltrating the entire affected area.
- Successful administration is often marked by a visible, immediate reversal of the tissue blanching.
- After injections are complete, apply warm compresses to the area to further promote vasodilation and drug dispersal.
Antidote #3: Dexrazoxane (Totect®) & Dimethyl Sulfoxide (DMSO)
Mechanism: Dexrazoxane is a catalytic inhibitor of topoisomerase II and an iron chelator. It is thought to protect tissue by preventing the formation of the DNA-damaging, iron-dependent free radicals that anthracyclines generate. DMSO is a free radical scavenger that can be applied topically.
Indicated for: Anthracycline chemotherapy agents (Doxorubicin, Daunorubicin, etc.).
Preparation & Administration:
- This is a systemic IV treatment, not a local injection. It is a multi-day infusion protocol.
- Dosing is based on the patient’s Body Surface Area (BSA).
- The first dose must be administered as soon as possible, ideally within 6 hours of the extravasation event.
- Crucially, cold compresses should be applied to the site before and between dexrazoxane infusions, and they should be removed at least 15 minutes before the infusion starts.
5.5 Your Ongoing Role: Documentation and Follow-Up
Closing the loop on a patient safety event.
Your responsibility does not end when the antidote is delivered. As the medication safety leader, you play a key role in the post-event process to ensure patient safety and promote system-wide learning.
- Meticulous Documentation: Write a detailed clinical note in the patient’s EHR. Document the time you were notified, the name of the drug, the estimated amount extravasated, the patient’s symptoms, the interventions taken (including antidote preparation and dispensing), and all communications with the nurse and prescriber.
- Safety Event Reporting: File a formal patient safety/incident report through your hospital’s reporting system. This is not for punitive purposes; it is essential for quality improvement. This data helps the institution identify trends, assess the frequency of extravasations, and develop better preventative strategies.
- Patient Monitoring: Continue to follow up on the patient’s progress. Is the site improving? Is the pain resolving? This demonstrates your commitment to the patient’s care and ensures no further intervention is needed.
- System Improvement: If a root cause analysis (RCA) is conducted, be an active participant. Was the extravasation due to an inappropriate line choice? Was there a knowledge gap? Your expert pharmacological perspective is vital to preventing the next event from occurring.
