Cytostatic agents extravasates T80.1

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Extravascular leakage or unintentional or erroneous administration of chemotherapy into the subcutaneous tissue or deeper tissue layers instead of the desired intravenous application. The consequences depend on the local effect of the cytostatic drug.

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In 0.1-05% of all intravenous cytostatic administrations.

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  • Choice of an unsuitable pharmaceutical form or access route
  • Error in the application technology
  • Patient related factors:
    • poor vein conditions due to repeated chemotherapy
    • advanced age with vein fragility
    • Phlebitis in the area of the injected vein
    • Reduction of venous return in cardiovascular diseases.

Clinical features
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  • Acute: Edema, redness, pain, hyperthermia.
  • Systemic reactions are possible.
  • Vasovagal reactions with nausea and vomiting.
  • Further course: From day 6-7 danger of necrosis! Possibility of superinfection.

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Therapy adapted to the causative agent.

General therapy
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  • Acute situation: Monitoring of pulse, local findings, vital signs; rapid initiation of therapy - even in the absence of symptoms.
    • Basic measures: Stop injection/infusion immediately, leave i.v. access for the time being, put on sterile gloves; aspirate as much extravasate as possible from the venous access with 5 ml syringe (dispose of syringe as cytostatic waste!); close venous access; aspirate contents of any blisters with tuberculin syringe and 27 G cannulas. Then remove the i.v. access.
    • Additional measures: Cover and fix the extravasated area with sterile compresses; elevate the extremity (24-48 hours), immobilize if necessary; inform the patient about further procedures; observe the extravasated area (at least 6 weeks).
  • Substance-specific measures (daunorubicin, doxorubicin, epirubicin):
    • In adults: if necessary, i.v. application of dexrazoxan (savena) once a day for three consecutive days.
    • Day 1: 1000 mg/m2 KO (max. 2000 mg), i.v. over 1-2 hours
    • Day 2: 1000 mg/m2 KO (max. 2000 mg), i.v. over 1-2 hours
    • day 3: 500 mg/m2 KO (max. 1000 mg), i.v. over 1-2 hrs.
    • Before dexrazoxan therapy, it must be clearly established that an anthracycline extravasate is present. In addition to the redness, local swelling is usually observed. Cave! Therapy costs (approx. 10.000 Euro for 3 days!).
    • In all cases where therapy with dexrazoxane is not indicated, the following measures apply to anthracycline extravasations:
      • Local cold applications every 4-6 hours for 15 minutes. Local application of 99% dimethyl sulfoxide (DMSO) with cotton wool carrier, repeat every 3-4 hours. Duration: 3-14 days depending on the clinic.
    • Cave! In case of liposomal daunorubicin or doxorubicin, use only local cold applications. No DMSO, because DMSO allows the release of anthracyclines from the liposomes and can lead to an increase of the damage potential.
    • Subject of the expert discussion are local application of a topical glucocorticoid and local infiltration with hyaluronidase.
  • Substance-specific measures (vinblastine, vincristine, vindesine, paclitaxel):
    • Local star-shaped (perilesional) injection with hyaluronidase (6-10 vials to 150 I.U. Dissolving the dry substance with 1.0 ml NaCl 0.9% per vial. Cave! Injecting the extravasation region causes strong, burning pain. Additional local analgesia with 2-5 ml of mepivacaine 1% should be considered. Local mild, dry heat application over 24 hours. (warm the extravasation site with a blanket!). Moist compresses should not be used, as there is a risk of maceration with promotion of necrosis tendency. The application of heat should be avoided with paclitaxel.
    • In discussion: For Vinca alkaloids: local infiltration of 8.4% NaHCO3 or sodium thiosulfate.

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  • Contents of the extravasation emergency kit:
    • 4 syringes 1 ml
    • 2 syringes 2 ml
    • 2 syringes 5 ml
    • 1 syringe 10 ml
    • 5 cannulas 27 G
    • 5 Combination closures
    • 4 pairs of sterile gloves (No. 6 + 7)
    • 5 x 2 cotton wool carriers sterile
    • 3 sterile compresses 5 x 5 cm
    • 3 sterile compresses 10 x 10 cm
    • 1 roll Leukosilk 2,5 cm
    • 1 Instant Cold Pack 10 x 20 cm . (to be stored in the fridge-freezer)
    • 1 Lavatherm heat pack 13 x 23 cm
    • 2 absorbent pads
    • 10 amps. Hyaluronidase 150 I.U. (store in refrigerator)
    • 8 amps. NaCl-Lsg. 0.9% 10 ml to dissolve
    • Two amps. MepiHexal sine 1% 5 ml (Mepivacaine HCl 50 mg)
    • 50 ml DMSO 99% pure (Merck)
    • Four amps. Savene 500 mg, plus 100 ml Aqua ad Injectabilia to dissolve and 1 btl. diluent 500 ml.
    • 2 syringes 50 ml, 4 cannulas 20G.

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  • For prevention, always ensure that the correct intravenous position of the access is maintained! In the case of cytostatics with a high probability of necrosis and in difficult vein conditions, timely port placement may be necessary. Due to the immediate reaction, the extent of the late damage is often not assessable. There are no validated guidelines for the treatment of extravasations. There are only expert recommendations.
  • Documentation: An extravasation and subsequent measures must be documented in any case.

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  1. Allwood M et al (1997) The Cytotoxics Handbook, pp. 107-121. 3rd Ed. Oxford and New York
  2. Mader I et al (2006) Extravasation of cytostatic drugs. A compendium for prevention and therapy. Springer Vienna New York.
  3. Mouridsen HT et al (2007) Treatment of anthracycline extravasation with Savene (dexrazoxane): results from two prospective clinical multicentre studies. Annals of Oncology 18: 546-550


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Last updated on: 29.10.2020