Management of noncytotoxic extravasation injuries: A focused update on medications, treatment strategies, and peripheral administration of vasopressors and hypertonic saline

Pharmacotherapy. 2023 Apr;43(4):321-337. doi: 10.1002/phar.2794. Epub 2023 Apr 1.


Extravasation is the leakage of intravenous solutions into surrounding tissues, which can be influenced by drug properties, infusion techniques, and patient-related risk factors. Although peripheral administration of vesicants may increase the risk of extravasation injuries, the time and resources required for central venous catheter placement may delay administration of time-sensitive therapies. Recent literature gathered from the growing use of peripheral vasopressors and hypertonic sodium suggests low risk of harm for initiating these emergent therapies peripherally, which may prevent delays and improve patient outcomes. Physiochemical causes of tissue injury include vasoconstriction, pH-mediated, osmolar-mediated, and cytotoxic mechanisms of extravasation injuries. Acidic agents, such as promethazine, amiodarone, and vancomycin, may cause edema, sloughing, and necrosis secondary to cellular desiccation. Alternatively, basic agents, such as phenytoin and acyclovir, may be more caustic due to deeper tissue penetration of the dissociated hydroxide ions. Osmotically active agents cause cellular damage as a result of osmotic shifts across cellular membranes in addition to agent-specific toxicities, such as calcium-induced vasoconstriction and calcifications or arginine-induced leakage of potassium causing apoptosis. A new category has been proposed to identify absorption-refractory mechanisms of injury in which agents such as propofol and lipids may persist in the extravasated space and cause necrosis or compartment syndrome. Pharmacological antidotes may be useful in select extravasations but requires prompt recognition and frequently complex administration strategies. Historically, intradermal phentolamine has been the preferred agent for vasopressor extravasations, but frequent supply shortages have led to the emergence of terbutaline, a β2 -agonist, as an acceptable alternative treatment option. For hyperosmolar and pH-related mechanisms of injuries, hyaluronidase is most commonly used to facilitate absorption and dispersion of injected agents. However, extravasation management is largely supportive and requires a protocolized multidisciplinary approach for early detection, treatment, and timely surgical referral when required to minimize adverse events.

Keywords: angiotensin II; catheterization; contrast media; extravasation of diagnostic and therapeutic materials; hyaluronidase; hypertonic solutions; iron; propofol; soft tissue injury; terbutaline; terlipressin; vasopressin; vasopressor agents.

Publication types

  • Review

MeSH terms

  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / therapy
  • Extravasation of Diagnostic and Therapeutic Materials* / epidemiology
  • Extravasation of Diagnostic and Therapeutic Materials* / prevention & control
  • Extravasation of Diagnostic and Therapeutic Materials* / therapy
  • Humans
  • Risk Factors
  • Saline Solution, Hypertonic* / administration & dosage
  • Saline Solution, Hypertonic* / adverse effects
  • Vasoconstriction
  • Vasoconstrictor Agents* / administration & dosage
  • Vasoconstrictor Agents* / adverse effects
  • Vasoconstrictor Agents* / therapeutic use


  • Vasoconstrictor Agents
  • Saline Solution, Hypertonic