2019.11.02 - 10am - Graham Klink - Handout

Graham Klink, PharmD November 2, 2019

10/30/2019

Extravasation Management:

A Hot Problem With Cold Solutions

Graham Klink, PharmD PGY2 Oncology Pharmacy Resident

Huntsman Cancer Institute

Disclosure

Relevant Financial Conflicts of Interest o CE Presenter, Graham Klink, PharmD

o None o CE Mentor, Erik Harrington, MS, PharmD, BCOP

o None o CE Mentor, Nannette Sageser, PharmD

o None

Off-Label Uses of Medications Sodium thiosulfate Phentolamine Hyaluronidase Dimethyl sulfoxide Nitroglycerin Terbutaline

Lexicomp. Wolters Kluwer, Inc. (2019)

Pharmacist Learning Objectives

Define vesicant, vesicant-like, irritant, and non-vesicant and their unique management when extravasated. Recognize risk factors for extravasation including iatrogenic causes, patient factors, and high-risk agents. Recall the pharmacology of agents used in the treatment of extravasation reversal. Construct an appropriate treatment regimen including both pharmacologic and non-pharmacologic options for the management of vesicant extravasation. Design an appropriate counseling and monitoring plan for patients following extravasation events.

Technician Learning Objectives

Identify antidotes used in the treatment of extravasation. Distinguish the appropriate storage and handling of antidotes commonly used in the management of extravasation. Recognize the proper compounding technique and appropriate dispensing of medications utilized in the management of various extravasation events.

Extravasation

Efflux of solutions from a vessel or direct infiltration into the surrounding tissues during intravenous infusion

Image: Goutos I et al. JHS (2014) 39E:08-18.

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Incidence and Outcomes

Extravasation of cytotoxic agents occurs at a rate of 0.01-6.5%

Incidence of non-cytotoxic agent extravasation is largely unknown

Majority occur in peripheral intravenous catheters (PIV)

Less common with central venous catheters (CVC)

Lesions may continue to expand and typically heal slowly

Ulceration may require plastic surgery or skin grafts Superimposed infection may occur Pain may persist for up to 1-2 weeks after extravasation

Goutos I et al. JHS (2014) 39E:08-18. Le A, et al. Annals of Pharma (2014)48(7):870-86.

Classification of agents

Vesicant ? capable of producing edema, pain, erythema, and potentially tissue ischemia and blistering

Vesicant-like ? usually classified as irritants but may cause local blistering, pain, and potential necrosis

Irritant ? transitory effect characterized by burning sensation, pain, and redness during the infusion or extravasation

Non-irritant - no local reactions, potentially mild inflammation or sensation of discomfort

Goutos I et al. JHS (2014) 39E:08-18. Kreidieh F, et al. WJCO (2016) 7(1) 87-97.

Classification of agents

Vesicants

Vesicant-like

Irritants

Non-vesicants

Vinca alkaloids Anthracyclines Alkylating agents Anti-tumor antibiotics Adrenergic agents Hyper/hyposmolar

agents

Taxanes Anti-tumor antibiotics

Alkylating agents Monoclonal antibodies

Platin Salts Topoisomerase II

inhibitors Alkylating agents Topoisomerase I

inhibitors Antibiotics Antiarrhythmics Liposomal Anthracyclines Antimetabolites

Arsenic Asparaginase Antimetabolites

Interferon Monoclonal antibodies

Bortezomib Antibiotics

Fidalgo J, et al. Annals of Oncol (2012) 23 (7) 167-73. Kreidieh F, et al. WJCO (2016) 7(1) 87-97.

Norepinephrine Epinephrine Dobutamine Dopamine Phenylephrine

Methylene Blue

Mitomycin Dactinomycin

Adrenergic agents

Platinums

Cisplatin 0.4 mg/mL

Hyperosmolar

Vesicants

Antitumor antibiotics

Other

Calcium chloride 10% Dextrose 10%

Potassium chloride 2 mEq/mL Sodium bicarbonate 8.4% Sodium chloride 3% Total Parenteral Nutrition

Acyclovir Phenytoin Promethazine

Doxorubicin Daunorubicin

Idarubicin

Anthracyclines

Vinca Alkaloids

Vincristine Vinblastine Vinorelbine

Fidalgo J, et al. Annals of Oncol (2012) 23 (7) 167-73. Kreidieh F, et al. WJCO (2016) 7(1) 87-97.

Le A, et al. Annals of Pharma (2014) 48(7) 870-86.

Oxaliplatin

Mitoxantrone

Bendamustine

Docetaxel

Vesicantlike

Ado- trastuzumab emtansine

Paclitaxel (conventional

& albumin bound)

Cabazitaxel

.

Kreidieh F, et al. WJCO (2016) 7(1) 87-97. Le A, et al. Annals of Pharma (2014) 48(7) 870-86.

Cladribine Cytarabine Fludarabine Fluorouracil Methotrexate

Daunorubicin liposomal Doxorubicin liposomal Daunorubicin liposomal- cytarabine liposomal

Antimetabolite

Liposomal Anthracyclines

Other

Topoisomerase I Inhibitors

Irritants

Antibiotics

Arsenic Bleomycin Bortezomib Brentuximab Etoposide

Topotecan Irinotecan

Amphotericin B Ganciclovir

Metronidazole Nafcillin

Vancomycin

Carboplatin 10 mg/mL

Cisplatin < 0.4 mg/mL

Platin Salts

Alkylating Agents

Busulfan Carmustine Cyclophosphamide Ifosfamide Melphalan

Fidalgo J, et al. Annals of Oncol (2012) 23 (7) 167-73. Kreidieh F, et al. WJCO (2016) 7(1) 87-97.

Le A, et al. Annals of Pharma (2014) 48(7) 870-86.

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Azacitidine Decitabine

Asparaginase

Cefepime Ceftriaxone Ceftazidime

Antimetabolites

Nonvesicants

Monoclonal Antibodies

Antibiotics

Interferon

Alemtuzumab Bevacizumab Ipilimumab Pertuzumab

Rituximab Trastuzumab

Boulanger J, et al. Sup Care Canc (2015) 23: 1459-71. Kreidieh F, et al. WJCO (2016) 7(1) 87-97.

Le A, et al. Annals of Pharma (2014) 48(7) 870-86.

Risk Factors

Patient Specific Factors

Iatrogenic Causes

Fragile, small, or mobile veins

Inexperienced personnel

Sclerosed veins

Multiple attempts at cannulation

Multiple courses of intravenous therapy Cannulation at an unsuitable site

Obesity

Infusion pumps

Impaired or altered circulation

Improper cannulation

Difficulty with communication

Prolonged infusion

Medication side effects

Pressure bag use

Goutos I et al. JHS (2014) 39E:08-18.

Preventing extravasation

Medical, pharmacy, and nursing team education and coordination Appropriate vascular access Appropriate cannula and needle selection Institution guidelines for extravasation

Image: Kreidieh FY et al. WJCO. (2016) 7:1.

Preventing extravasation

Proper administration of vesicant drugs

Use central line when possible Recent placement of line Avoid dorsum of hand or near joints Do not cover cannula entry site Do not test with cytotoxic drug Flush line every 2-3 minutes

Midline Catheter

Image: Ener R.A., et al. Annals of Oncol (2004) 15; 858-62.

Kreidieh FY et al. WJCO. (2016) 7:1.

Preventing extravasation

Patient Education

Risk of extravasation Accurate history of previous extremity manipulation Report discomfort, pain, redness or swelling immediately Understand risk associated with PIV versus CVC

Ener R.A., et al. Annals of Oncol (2004) 15; 858-62. Kreidieh FY et al. WJCO. (2016) 7:1.

Diagnosis of Extravasation

Patient symptoms

? Tingling, burning, discomfort, pain, swelling or redness

Nursing staff education

? Frequently monitoring for swelling, redness, blanching, absence of

blood return, or resistance during bolus administration

Differential Diagnosis

?LocalLsokincarelacrteioansction vs. chemicaClhepmhiclaelbphitleibsitviss. extravasation

Asparaginase Cisplatin Daunorubicin

Doxorubicin Fludarabine Melphalan

Carmustine Cisplatin 5-FU

Gemcitabine Vinorelbine

Fidalgo P et al. Annals o Oncol (2012) 23(7):167-173.

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? Blanched skin ? Edema < 1 inch ? Cool to touch ? With or without pain

? Same as Grade 1 ? Edema 1-6 inches

Grade 1

Grade 2

Staging of Extravasation

? Tight, leaking skin ? Discolored, bruised, or

deep pitting edema ? Moderate to severe pain ? Circulatory impairment ? Irritant or vesicant

Grade 4

Grade 3

? Blanched or translucent skin

? Edema > 6 inches ? Mild to moderate pain ? Possible numbness

Image: Reynolds P, et al. Pharma (2014) 34(6) 617-32.

Management Principles of Extravasation

Immediate Management General Management Specific Management

Immediate Management of Peripheral IV Extravasation

STOP the infusion AND DISCONNECT the infusion set

LEAVE the needle in place and ASPIRATE as much fluid as possible

DO NORTErMemOVoEvethneeecadnlenufolar cainsdplMatAinRK0t.h4emegx/tmravLaosratbeednadraemaustine

Goutos I et al. JHS (2014) 39E:08-18.

Immediate Management of Central IV Extravasation

STOP the infusion AND DISCONNECT the infusion set

LEAVE the central line in place and ASPIRATE extravasated fluid

URGENT Chest X-ray or thoracic computed topography (CT) imaging and CONSULT surgery

Fidalgo P et al. Annals o Oncol (2012) 23(7):167-173.

Contact the Provider Immediately

Image:

General Management

MONITOR every 5-10 minutes for altered mental status and any significant skin changes

APPLY DRY compresses for 15 minutes every 6 hours

Localize and neutralize

Anthracyclines, antibiotics, taxanes, cisplatin 0.4 mg/mL, and alkylating agents

Disperse and dilute Vinca alkaloids, oxaliplatin, and sympathomimetic agents

Fidalgo P et al. "ESMO". Annals o Oncol (2012) 23(7):167-173.

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General Management ? Documentation

Patient Name Date and Time Name of Drug and MRN Extravasation and Diluent

Description of Intravenous

Access

Amount of Drug

Extravasated

Location and Size of

Extravasation

Fidalgo P et al. Annals of Oncol (2012) 23(7):167-173. Mullin S, et al. Hospital Pharmacy (2000) 35:57-76.

General Management ? Documentation

Erythema, Swelling, and

Induration

Presence or Absence of

Pain

Record Pain Management

Steps

Other Agents Administered

Include Photographs if

Possible

Continue to Document Progression

Fidalgo P et al. Annals of Oncol (2012) 23(7):167-173. Mullin S, et al. Hospital Pharmacy (2000) 35:57-76.

Pharmacology Specific Management

1. Vasoconstriction/ Ischemic Necrosis 2. Direct Toxicity 3. Osmotic Damage 4. Extrinsic Mechanical Compression

Goutos I et al. JHS (2014) 39E:08-18.

Extravasation of Sympathomimetic Agents

Mechanism

Local stimulation of -adrenergic receptors may lead to tissue ischemia

Agents

Dobutamine, Dopamine, Epinephrine, Norepinephrine, and Phenylephrine

Specific Management

Warm compress, Phentolamine, Terbutaline, and Nitroglycerin Ointment

Le A, et al. Annals of Pharma (2014) 48(7) 870-86.

Extravasation of Sympathomimetic Agents

Age < 2 years old

Age 2 years old

Nitroglycerin ointment

Phentolamine

Use terbutaline/ nitroglycerin only when on shortage or contraindicated

Terbutaline

Le A, et al. Annals of Pharma (2014) 48(7) 870-86. Plum M et al. Pharm and Thera (2017) 42(9) 581-85.

Antidotes for Sympathomimetic Agents Phentolamine

Non-specific -receptor antagonist, competes with catecholamines to reverse ischemia

Phentolamine 2 receptor 1 receptor

Le A, et al. Annals of Pharma (2014) 48(7) 870-86.

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