Sodium thiosulfate MOA: neutralizes reactive species and reduces formation of hydroxyl radicals that can cause tissue injury Used for cisplatin, cyclophosphamide, mechlorethamine, dacarbazine, alternative for hyperosmolar agents, alternative for calcium.
Use 2 mL of the prepared solution for each 1 mg drug extravasated Use a gauge needle to inject SC to the affected area change needle with each injection Hyperosmolar extravasations severe : DMSO MOA: scavenges free radicals and has anti-inflammatory, analgesic, and vasodilatory effects which promote systemic absorption of drug Used for mitomycin, dactinomycin, mitoxantrone and possible alternative for anthracyclines.
Apply topically to site for 7 to 14 days and allow to dry Do not cover application site with a dressing. Use a gauge needle to inject at multiple sites within the affected area change needle with each injection Administer within 12 to 13 hours of the injury.
Nitroglycerin topical MOA: increases nitric oxide, promoting vasodilation Used for vasopressors alternative to phentolamine , hyperosmolar agents, methylene blue. Use a gauge needle to inject locally across symptomatic sites change needle with each injection. Preferred : Phentolamine for most agents; topical nitroglycerin ointment for vasopressin and methylene blue Alternative: Topical nitroglycerin ointment, terbutaline.
Preferred : Hyaluronidase Alternative for calcium : Sodium thiosulfate Alternative for total parenteral nutrition : some authors suggest topical nitroglycerin ointment. Other Amphotericin Metronidazole Penicillin Valproate. Common symptoms and signs of extravasation include pain, stinging or burning sensations, and edema around the intravenous IV injection site. To prevent extravasation, a clinical specialist should perform the venipuncture or injection, who with relevant skills and management ability understands the properties of the injected drug.
The primary purpose of these guidelines is to minimize the side-effects of IV injection, by suggesting proper and prompt emergency measures for extravasation and the appropriate treatments corresponding to the properties of the injected drug. These guidelines consist of following topics: basic knowledge about extravasation, extravasation management, and extravasation prevention.
Antidotes, special drug management, drugs with high osmolarity, and drugs with pH are provided as supplement files Supplements 1 — 4. It is anticipated that these guidelines would help health professionals to prevent extravasation during IV and central vein injection and to promote patient safety should extravasation occur in any case. Extravasation is the leakage of an injected drug out of the blood vessels, damaging the surrounding tissues. In terms of cancer therapy, extravasation refers to the inadvertent infiltration of chemotherapeutic drugs in the tissues surrounding the IV site.
The frequency of extravasation in adults is reported to be between 0. Some data suggest that the incidence is decreasing probably due to improvements in the infusion procedure, early recognition of the drug leakage, and training in management techniques. Risk factors can be classified under patient-related, procedure-related, and product or product-related factors. Patients must be informed to report any changes in sensation, signs, or symptoms during the IV administration of any chemotherapeutic drug and to alert the healthcare professionals to early signs of extravasation.
Particular information must be given when a vesicant drug is administered. Extravasation must be suspected if any of the following specific signs or symptoms are presented Table 1. Spots or solid lines with blisters can be suddenly felt along the vessels injected with drugs. Pain, edema, and ulcer do not appear, and symptoms disappear within 30 to 90 minutes. Pain, tightening, and skin discoloration tend to worsen. Blood backflow works well, and edema or ulcer do not occur.
Pain or tightening occurs along the vein, and it is caused mainly by drugs such as vinorelbine and dacarbazine. Hot fomentations can be applied to the dilated veins to mitigate the symptoms. Occurs due to contraction of the vessel wall and usually happens as soon as the fluid injection begins.
For the most part, blood does not backflow. Discoloration and edema do not occur. Venous shock can occur when injecting very cold medication or when medication is injected at a rapid pace. Hot fomentations can dilate the veins and mitigate the symptoms. While the injury is usually minor and resolves spontaneously, some cases result in serious complications, including full-thickness skin loss and muscle and tendon necrosis requiring reconstructive surgery or even amputation, leading to longer hospital stays, increased morbidity, and increased costs.
Narcotic analgesics may be required to reduce severe pain around widespread extensive necrosis. Depending on the situation, patients will bear the cost of hospitalization and medical expenses for cosmetic surgeries, and secondary medical problems might occur if the condition worsens.
Treatment suspension wastes time and other problems can occur due to delayed treatment. If bone marrow function decreases, anticancer treatments may be delayed due to infection caused by leukopenia. Therapists will always feel nervous during the medical team-patient communication because of guilt. Communication and trust between patients and nurses can be interfered due to extravasation.
At the first sign of extravasation, the following steps are recommended: 1 stop administration of IV fluids immediately, 2 disconnect the IV tube from the cannula, 3 aspirate any residual drug from the cannula, 4 administer a drug-specific antidote, and 5 notify the physician Fig.
Elevation of the limb may aid in reabsorption of the infiltrate or extravasated vesicant by decreasing capillary hydrostatic pressure. Apply sterile dressing over the area of extravasation, regularly assess the extravasation site during every shift, and take medical photographs and consult the department of cosmetic surgery if necessary.
Cold application is recommended for extravasation of DNA-binding vesicants except for mechlorethamine nitrogen mustard , contrast media, and hyperosmolar fluids. The use of local warming therapy dry heat is based on the theory that it enhances vasodilation, thus enhancing the dispersion of the vesicant agent and decreasing drug accumulation in the local tissue.
The use of local warming is recommended for the extravasation of non—DNA-binding vesicants. Although clear benefit has not been demonstrated with thermal applications, it remains a standard supportive care, and the recommended application schedule for both warm and cold applications is 15 to 20 minutes, every 4 hours, for 24 to 48 hours. Because errors associated with IV administration can result in fatal or life-threatening outcomes, administration of IV fluids and medications can be a high-risk, with adverse outcomes potentially leading to malpractice claims.
Cochrane Database of Systematic Reviews , Issue DOI: Al-Benna, S. Extravasation injuries in adults. ISRN dermatology, , Journal of Infusion Nursing, 34 4 , pp.
Beall, V. Newborn and Infant Nursing Reviews, 13 4 , pp. Emergency treatment of accidental infusion leakage in the newborn: report of 14 cases. British Journal of Plastic Surgery.
International Journal of Surgery, 12 10 , pp. Corbett, M. BMC Pediatr, 19 1 , pp. Preventing the scars of neonatal intensive care. Archives of disease in childhood. Patients may require the use of analgesics to help manage the pain they may experience. For vinca alkaloids, where dispersal or dilution of the vesicant is indicated, apply local heat for 20 minutes 4 times daily for 1 for 2 days.
For other vesicant extravasations, including anthracyclines, initial treatment is geared toward localizing and neutralizing the extravasated agent with cold compresses for 20 minutes 4 times daily for 1 to 2 days, limiting the cellular uptake of these agents.
DMSO: DMSO is a common solvent that penetrates tissues and enhances skin permeability, which may facilitate absorption of an extravasated drug. This solution is FDA approved only for the treatment of recurrent interstitial cystitis. In one case, a mg daunorubicin extravasation in a year-old man was treated with sodium bicarbonate, dexamethasone 4 mg , ice packs, and 1.
This regimen provided pain relief and ulcer prevention. The patient also received sodium bicarbonate 8. In another case, a year-old man receiving 4 to 6 mg of doxorubicin was treated for extravasation of doxorubicin with 5 mL of 8. Ulceration did not occur; however, a 3 x 2. Berghammer et al also reported a case of docetaxel extravasation. DMSO was applied 3 times every 45 minutes, and oral corticosteroids and diclofenac were given on the day of extravasation.
All symptoms resolved within 24 hours; however, delayed symptoms brown discoloration, skin hyperplasia appeared on day 5 and increased thereafter. No plastic surgical intervention was necessary.
Although DMSO in combination with hypothermia and isotonic saline solution was not effective in preventing the delayed symptoms, it did restrict the inflammation and tissue necrosis.
Bertelli also conducted a prospective study evaluating the effects of DMSO on anthracycline extravasations. In these case reports and small studies, extravasations were diagnosed clinically and not by biopsy.
DMSO may be an option for the treatment of extravasated anthracyclines, mitomycin C, and actinomycin D. It is recommended that a thin layer of DMSO be applied to the extravasated area and allowed to dry. A nonocclusive dressing should be applied within 10 to 25 minutes.
These steps should be repeated every 8 hours for 7 days. Hyaluronidase: It is thought that hyaluronidase is able to break down the extracellular matrix that underlies epithelial cells. The matrix holds on to large amounts of water molecules, and upon its breakdown, it is able to release the fluid into the extracellular milieu.
In the case of an extravasation, it allows for increased fluid to the site, thus diluting the actual concentration of the skin at the site of contact. No steroids or cold packs were applied. Pain resolved within days of treatment with hyaluronidase in all patients.
One patient complained of mildly painful induration 3 months after the extravasation of vincristine. More prospective trials must be conducted. Sodium Thiosulfate: Sodium thiosulfate prevents alkylation and tissue destruction by providing a substrate for alkylation in the subcutaneous tissue. Sodium thiosulfate has been demonstrated to be effective in animal experiments and in one case report for the treatment of mechlorethamine nitrogen mustard extravasation.
Due to lack of evidence, the EONS extravasation guidelines do not recommend this as an antidote. Dexrazoxane: Dexrazoxane Totect was recently approved by the FDA for the treatment of anthracycline-induced extravasations. Dexrazoxane has a dual mechanism of action: 1 it acts as an iron chelator, preventing formation of iron-anthracycline complexes and iron-mediated hydroxyl radicals that cause oxidative damage; and 2 it stabilizes topoisomerase II and makes it inaccessible to anthracycline chemotherapy.
Dexrazoxane blocks the enzyme so that it is no longer affected by anthracycline and prevents damage to the healthy cells in tissue. Dexrazoxane efficacy was demonstrated in two clinical trials conducted in Europe.
The first study enrolled patients from 17 cancer sites in Denmark, and the second enrolled patients from 34 cancer sites in Denmark, Germany, Italy, and the Netherlands.
Anthracycline extravasation was diagnosed and confirmed via fluorescence microscopy of biopsied tissue taken within 6 hours of dexrazoxane. The primary end point was the rate of surgical resection and necrosis. Patients were assessed for efficacy and safety at days 7, 14, 21, and 28, and for efficacy at day The mean extravasation area was Eleven patients had areas of extravasation exceeding 75 cm 2.
There were no incidences of surgery in study 1 and 1 incident 2. The patient who developed tissue necrosis due to extravasation had a very large area of doxorubicin extravasation measuring cm 2. In study 1, there was 1 5.
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