Chief Complaint:

Calcium Burns

HPI:

46 year old male with past medical history of ESRD on HD, hypertension, congestive heart failure and secondary hyperparathyroidism underwent a subtotal parathyroidectomy without complications 18 days ago. Pt had extravasation of IV calcium chloride infusion to his right forearm 17 days ago; hand surgery was consulted and recommended warm soaks. He was discharged home on post-operative day #4. He now presents with right arm pain localized to the wound. Over the last 3 days, he developed new blisters around the wound with worsening pain and swelling. He reports that the wound has not grown in size. The pain is worse with flexion and extension of the wrist and fingers. Pt also reports chills. Initially, the patient had relief with Percocet, but not over the last 3 days.

Pertinent Exam Findings:

Labs: HR:104 BP:212/131 Resp:22 Pulse Ox: 90% on 2L
Cardiac: Radial pulse 2/4
Skin: Roughly 10×6 cm painful area with hemorrhagic bullae on the borders, on the right dorsal forearm, tenderness over the wound, central area with eschar about the size of dime, soft compartments
Neuro: Radial, Ulnar, Median Nerve intact to light touch

Data Interpretation:

Lactic acid 2.2 elevated.
CBC: There is no acute leukocytosis, unstable anemia, or significant platelet abnormality.
BMP: There is CKD consistent with end stage renal disease and hyperkalemia to 5.6.

Imaging:
Right Forearm xray:
IMPRESSION: Negative for acute bony abnormality. Soft tissue swelling. No foreign body. No soft tissue emphysema.

ED Course:

Ancef, Dilaudid, IV Fluids, Zofran

Hand was consulted and recommended NPO OR for debridement of right arm.

Hospital Course:

Went to OR with excision of right forearm down to fascia and application of cadaver allograft, patient will eventually require a split thickness skin graft for definitive reconstruction. Discharged on post-operative day 1.

DISCUSSION:

Background:

Intravenous calcium has several uses but it is commonly used in the ED to stabilize the cardiac myocyte membranes in patients with hyperkalemia, treat hypocalcemia and calcium channel blocker toxicity. Calcium is also given for hypocalcemia secondary to vitamin D deficiency and hypoparathyroidism, which can be potentially lethal. Intravenous calcium is given in two forms, calcium chloride or calcium gluconate. Extravasation of any calcium-containing peripheral IV can lead to erythema, tenderness, induration, edema and in the worst cases skin necrosis of the infusion site and surrounding tissue.

Calcinosis cutis or calcium-induced extravasation injury occurs when calcium salts infiltrate the skin and surrounding tissue. The exact pathophysiology of calcinosis cutis is not fully understood. Multiple mechanisms have been proposed including local inflammatory responses and tissue necrosis through vasoconstriction of capillaries and intracellular fluid retention, leading to deep tissue damage and late-onset calcifications.

Calcium chloride, has a higher risk of adverse effects including skin necrosis from extravasation compared to calcium gluconate. This is thought to be due to increased risk from calcium chloride having a greater dissociation and thus elevated local ionized calcium concentration which is of greater clinical significance than other factors such as pH or osmolarity. Also, due to the size of the sugar moiety, an ampule of calcium gluconate has approximately 1/3 the volume of calcium when compared to an ampule of calcium chloride.

The exact prevalence of extravasation-induced necrosis due to intravenous calcium is unknown. Prior studies have reported an extravasation incidence in chemotherapy or cytotoxic vesicants infusions ranging 0.01% and 6% and a case series examining children reported a 0.24% of skin injury linked to extravasation. It is unknown which cases of calcium extravasation will progress to necrosis, but there have been enough occurrences of calcium extravasation-induced skin necrosis that providers should keep it in mind when administering calcium intravenously.

Diagnosis:

Diagnosis of calcium-induced extravasation injury or necrosis is clinical and correlated with a history of calcium chloride infusion. The patient may report pain at the infusion site and there may be signs of local edema or induration. Recognition of extravasation and prompt discontinuation of the intravenous infusion is key to stopping continued infiltration of the surrounding tissue.

Early necrotic tissue will have erythematous subcutaneous nodules with overlying bullae. Areas of necrosis can develop over a period of days to weeks and develop induration and ecchymosis. Late lesions can become ulcerated and eschars may develop. Secondary infections may develop and risk increases with more extensive necrosis.

Management in ED:

Prevention of extravasation is of utmost importance in prevention of calcium-induced skin necrosis. Using a central line is highly recommended, especially for calcium chloride. If extravasation of a calcium is suspected during infusion, stop the infusion first and foremost. Then aspirate the cannula and avoid applying pressure to the area as you elevate the extremity. Any effusion in the subcutaneous tissue should be drained via the cannula. After these steps, application of a cold pack to the area may help reduce spread in local tissue via vasconstriction.

There have been some studies that looked at hyaluronidase and intralesional triamcinolone which were of benefit in mice and rabbit models but this has not been proven in humans.

For subacute calcium-induced extravasation injury, management is going to be based on the extent of the injury. Pain management should be prioritized after initial evaluation given the severe pain that can occur with this type of injury. The patient should be evaluated for a concomitant abscess or cellulitis as well. If necrotic tissue or extensive ulcers are present on exam, surgical debridement is necessary and the appropriate surgical service should be consulted. For deep partial-thickness or full-thickness necrosis, a split-thickness skin graft may be required.

Prognosis:

Local necrosis from extravasation of calcium may heal with conservative management alone, but may progress to eschar formation or tissue ulceration that requires surgical debridement and skin graft. More intermediate outcomes consist of chronic pain, cosmetic skin changes, or decreased function secondary to contractures or neuropathy.

Differential Diagnoses:

• • Cellulitis
  • Abscess
  • Lymphangitis
  • Neuropathic pain
  • Allergic dermatitis
  • Necrotizing soft tissue infections
  • Osteomyelitis

Clinical Pearls:

• • Keep in mind the risks of calcium extravasation-induced skin necrosis when giving calcium chloride in the ED.
  • CaCl is greater risk than calcium gluconate for necrosis and a central line should be used whenever possible for CaCl
  • For acute extravasation injury, stop the infusion and conservatively manage to minimize tissue damage.
  • For subacute extravasation injury, necrotic tissue or extensive ulceration will likely need surgical debridement.

References:

1. Fong J, Khan A. Hypocalcemia: updates in diagnosis and management for primary care. Can Fam Physician. 2012;58(2):158-162.
2. Valenzuela, Antonia, Chung, Lorinda. Calcinosis: pathophysiology and management. Curr Opin Rheumatol. 2015;27(6):542-548. doi:10.1097/BOR.0000000000000220.
3. Hannon MG, Lee SK. Extravasation injuries. J Hand Surg Am. 2011 Dec;36(12):2060-5; quiz 2066. doi: 10.1016/j.jhsa.2011.10.001. PMID: 22123049.
   
4. David V, Christou N, Etienne P, et al. Extravasation of Noncytotoxic Drugs. Annals of Pharmacotherapy. 2020;54(8):804-814. doi:10.1177/1060028020903406
5. Al-Benna S, O’Boyle C, Holley J. Extravasation injuries in adults. ISRN Dermatol. 2013;2013:856541. Published 2013 May 8. doi:10.1155/2013/856541
6. Lin CY, Hsieh KC, Yeh MC, Sheen-Chen SM, Chou FF. Skin necrosis after intravenous calcium chloride administration as a complication of parathyroidectomy for secondary hyperparathyroidism: report of four cases. Surg Today. 2007;37(9):778-81. doi: 10.1007/s00595-006-3426-z. Epub 2007 Aug 27. PMID: 17713732.
7. Ahn SK, Kim KT, Lee SH, Hwang SM, Choi EH, Choi S. The efficacy of treatment with triamcinolone acetonide in calcinosis cutis following extravasation of calcium gluconate: a preliminary study. Pediatr Dermatol. 1997 Mar-Apr;14(2):103-9. doi: 10.1111/j.1525-1470.1997.tb00214.x. PMID: 9144694.
8. Pacheco Compaña FJ, Midón Míguez J, de Toro Santos FJ, Centeno Cortés A, López San Martín P, Yebra-Pimentel Vidal MT, Mosquera Osés JJ. The Use of Antidotes for Calcium Gluconate Extravasation: An Experimental Study in Mice. Plast Reconstr Surg. 2018 Sep;142(3):699-707. doi: 10.1097/PRS.0000000000004640. PMID: 29927835.

Authors

Aaron Wolfe, DO, FACEP

Jackson Roos, MSIV

John Spartz, MSIII