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Addressing Lower Extremity Ischemia Issues After The Use Of Vasopressors

Discussing the case of a 65-year-old female patient who developed digital ischemia and subsequent bilateral gangrenous changes in the feet after vasopressor use, these authors review key considerations in facilitating successful limb salvage. 

Too often, patients present to the emergency department (ED) with unstable vitals and are suffering from septic shock. Some patients who are unresponsive to resuscitative therapy subsequently begin vasopressor therapy with immediate intensive care unit admission. After several days, once patients stabilize, intensivists wean them from the vasopressor therapy. However, these patients often develop peripheral extremity necrosis, an adverse effect of these drugs, and face amputation or limb loss. This scenario is unfortunately common. However, there is no current podiatric literature regarding the role of the foot and ankle surgeon for limb salvage in the setting of vasopressor therapy. 

There are an estimated 5.6 million cases of hypotension and one million cases of septic shock that present to United States emergency departments each year.1 Shock is a biologic response in which perfusion to the tissues does not meet the demand for oxygen. The main goal in treating shock is to increase oxygen delivery. This can require a high dose of vasopressor therapy to maintain blood volume until one can achieve source control of the infection.2 

Physicians frequently use dopamine and noradrenaline for the treatment of septic shock.3 Dopamine is a neurotransmitter that acts on dopaminergic and adrenergic receptors to elicit an increase in cardiac contractility.4 High doses of dopamine can result in vasoconstriction.5 Noradrenaline is an alpha-receptor stimulator and its vasospastic effect can have an intense effect in the digital vascular beds.2 It is a first-choice agent that acts as a vasopressor and increases myocardial contractility in cardiogenic shock.2 Therefore, when physicians employ pharmacological agents like dopamine and noradrenaline in high doses or for a prolonged period of time in patients with septic shock, this may lead to peripheral gangrene in these patients.5 

When there is systemic peripheral gangrene, a patient may or may not have normal pedal pulses and acute thrombi develop in the small arteries.6 Nema and colleagues maintain that systemic peripheral gangrene is a rare and severe complication of disseminated intravascular coagulation (DIC), which is frequently associated with sepsis.6 Unfortunately, there is no definitive way to treat this sequela other than amputation of the necrotic digits or limbs. In addition to surgical excision of the avascular tissue, antibiotic and supportive therapy can improve systemic and peripheral perfusion.7 

We work within a hospital system that admits a significant number of patients to the intensive care units for septic shock. The podiatric surgical service often provides consults for evaluation and surgical management when the digits begin to show ischemic skin changes. With this in mind, let us take a closer look at a case involving systemic peripheral gangrene in an effort to shed light on this condition in the hospital system-based podiatric community. 

When A Patient Presents With Two Months Of Post-Vasopressor Gangrenous Changes To The Feet

A 65-year-old female patient presented at an outside hospital with abdominal pain for several days. During her hospitalization, she received a diagnosis of left pyelonephritis complicated by E. coli bacteremia, experienced acute tubular necrosis that briefly required hemodialysis, atrial fibrillation, upper gastrointestinal bleed, pulseless electrical activity (PEA) cardiac arrest as well as C. difficile infection. While admitted, the patient went into septic shock, requiring intensive care unit (ICU) admission, along with intubation and use of vasopressors. During her ICU admission, the patient initially received norepinephrine (Levophed) 8 mg/250 mL (32 mcg/mL) in D5W infusion (0.5-30 mcg/min) and vasopressin (Vasostrict) infusion 0.4 unit/ml. Intensivists titrated the medications as necessary, based on the patient’s systemic medical demands. She fully weaned off the vasopressors on day five of her ICU admission. 

Unfortunately, due to the prolonged use of vasopressors, the patient developed bilateral upper and lower extremity ischemia, mostly to all her toes and fingers. The outside facility consulted vascular surgery for the upper and lower extremity ischemia, and vascular surgery recommended discontinuation of pressors as able, as well as local wound care until full demarcation occurred. There was no surgical intervention during the patient’s initial hospitalization. After the patient stabilized, the patient was transferred to an outside acute rehabilitation facility. During her rehabilitation, she had persistently low blood pressure over a two-week time frame. Instead of transfer back to the initial evaluating hospital, she went to our hospital for further evaluation due to proximity to the rehabilitation facility.

Once this transfer took place (two months since her initial presentation at the outside hospital), the patient had swift treatment for her current medical conditions. The podiatry service received a consult for further management of the patient’s bilateral lower extremity gangrenous changes. Based on initial evaluation, there was a concern for limb salvageability, specifically for the left foot in comparison to the right. Both feet had demarcated with dry/stable gangrenous changes to approximately the midfoot level without clinical signs of infection. The patient had readily palpable dorsalis pedis and posterior tibial pulses on examination as the etiology of her gangrene was secondary to vasopressor use. 

Vascular surgery provided a second opinion regarding the patient’s prognosis and suggested bilateral proximal below-knee amputations. However, the patient and her family decided to pursue limb salvage. They understood that limb salvage could take months of treatment and required strict patient adherence, but the patient expressed determination to save as much of her limbs as possible. 

Shortly after the initial consultation, we brought the patient to the operating room for bilateral open midfoot amputations with tendo-Achilles lengthening. We also initiated negative pressure wound therapy (NPWT) to assist in granulation tissue formation. The patient experienced no surgical complications. 

After the patient’s hospitalization, she continued NPWT three times a week at an acute rehabilitation facility with close outpatient follow-up. The patient was extremely adherent with follow-up and local wound care. As more granulation tissue filled in, bilateral areas with exposed bone persisted. In February 2020, we brought the patient back to the operating room for further excisional debridement of soft tissue and bone with application of Integra Bilayer Matrix graft. She did well post-operatively and resumed outpatient negative pressure wound therapy and close follow-up. She continues to present to clinic regularly with twice-weekly NPWT changes as well as topical collagenase application to the fibrotic regions of her amputation sites. The treating clinician and patient anticipate that in the upcoming months, she will make a full recovery. 

Recognizing the Serious Ramifications Of Digital Ischemia After Vasopressor Use          

More often than not, adverse effects of vasopressor use emerge in the ICU but very few publications discuss the long-term management of digital ischemia, specifically in the lower extremity, in these patients. 

Below are other examples of patient consultations seen by the podiatric service at our institution with concern for acute lower extremity ischemia secondary to vasopressor use. Some patients had reversible ischemia and did not require amputation while many unfortunately progressed to partial foot amputations or proximal amputations (below-knee versus above-knee) depending on the rest of their comorbidities and prognosis. For many of these patients, combating the severe systemic illness was a far greater battle than tackling limb ischemia. However, it is important to take note of the devastating side effects of vasopressors. Accordingly, when these patients stabilize, one can provide timely treatment of their limb ischemia/gangrene while also preparing the patients for the potential outcome of limb loss. 

In Conclusion

When patients are in septic shock, getting perfusion to their vital organs becomes the utmost priority. However, when patients return to their normal baseline function and there is eradication of infection, some must come to the unfortunate realization that extraordinary measures performed to sustain life may have led to lower extremity ischemia. Individuals with otherwise no vasculopathy and intact pulses then watch their digits or extremities turn dusky and eventually necrose. 

Although this is not the case for every patient who undergoes vasopressor therapy, one should be aware of this condition. Full demarcation must occur before one formulates a surgical plan. If a patient is intubated, treating physicians should make the patient’s family members aware of the possible outcome of peripheral gangrene. The foot and ankle surgical community should treat these patients with profound empathy and come up with salvage or reconstructive plans that allow for the best functional outcome.  

By having a strong awareness of the adverse result of vasopressor therapy, podiatrists should be prepared to take on the challenge of limb salvage after the intensivists eliminate the threat of loss of life. 

Dr. Magodia is a fourth-year resident at the Temple University Hospital Podiatric Surgical Residency Program in Philadelphia.

Dr. Mateen is a third-year resident at the Temple University Hospital Podiatric Surgical Residency Program in Philadelphia.

Dr. Pontious is a Clinical Professor in the Department of Podiatric Surgery at Temple University School of Podiatric Medicine in Philadelphia. 

Online Exclusives
By Spruha Magodia, DPM, Sara Mateen, DPM, and Jane Pontious, DPM, FACFAS

1. Puskarich MA, Jones AE. Sepsis. In: Tintinalli J, Ma OJ, Yealy DM, et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide. (6th ed) New York: McGraw Hill Professional; 2010:1-21. 

2. Levy J, Ghadimi K, Faraoni D, et al. Ischemic limb necrosis in septic shock: What is the role of high-dose vasopressor therapy? J Thromb Haemost. 2019;17(11):1973-1978. https: // 

3. Ang CH, Koo OT, Howe TS. Four limb amputations due to peripheral gangrene from inotrope use – case report and review of literature. Int Surg J Case Rep. 2015;14:63-65. 

4. Overgaard CB, Dzavik V. Review of physiology and clinical use in cardiovascular disease. Circulation. 2008;118:1047-1056. 

5. Kaul S, Sarela AI, Supe AN, Karnard DR. Gangrene complicating dopamine therapy. J R Soc Med. 1997;90(2):80.

6. Nema AA, Darshan JR, Iyer S. Digital gangrene in patients with sepsis. Int Surg J. 2018:5(5):1673-1676.

7. Akamatsu S, Kojima A, Tanaka A, Hayashi K, Hashimoto T. Symmetric peripheral gangrene. Anesthesiology. 2013;118(6):1455. 


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