This report describes the case of a female dog that developed extensive necrosis in the pelvic limbs as a result of peripheral extravasation of norepinephrine, a potent vasopressor associated with intense vasoconstriction, local ischemia, and severe tissue injury. The progression of the condition resulted in significant structural impairment, culminating in a pathological fracture secondary to tissue necrosis. Peripheral administration of this drug is recognized as a high-risk factor for local complications, especially in emergency settings in which central venous access is not always readily available. The therapeutic management consisted of a multimodal approach, including ozone therapy, low-level laser therapy, and advanced dressings using Curatec technology, aiming to modulate inflammation, stimulate angiogenesis, and promote tissue regeneration, and this approach was maintained even after the fracture occurred. A progressively favorable clinical evolution was observed, with reduction of necrosis, recovery of skin integrity, and functional improvement of the affected limbs. This case highlights the importance of early recognition of vasopressor extravasation, strict monitoring of peripheral venous access sites, and immediate implementation of adjuvant therapeutic strategies in the management of catecholamine-induced ischemic injuries, as well as in the prevention of secondary orthopedic complications.

Maintenance of systemic arterial blood pressure is essential to ensure adequate tissue perfusion and cellular oxygenation in critically ill patients, and it is one of the main determinants of prognosis in cases of circulatory shock (Bozza et al., 2010; Vincent; De Backer, 2013). When fluid resuscitation alone is not sufficient to restore hemodynamic stability, the use of vasoactive drugs becomes indispensable, with emphasis on vasopressors, which are widely used in both human medicine and veterinary intensive care (Silverstein; Hopper, 2015; Murphy; Rishniw; Silverstein, 2022).

Among the available agents, norepinephrine is currently recommended as the first-line vasopressor in different types of shock, especially septic shock, according to international guidelines for the management of critically ill patients (Dellinger et al., 2013; Singer et al., 2016; Evans et al., 2021). Its mechanism of action is based predominantly on stimulation of alpha-adrenergic receptors, promoting effective peripheral vasoconstriction, increased systemic vascular resistance, and consequent elevation of arterial blood pressure, with a lower chronotropic effect when compared with other vasopressors (Silverstein, 2006; Vincent; De Backer, 2013).

Experimental and clinical studies support the hemodynamic efficacy of norepinephrine. Minneci et al. (2004) demonstrated greater cardiovascular stability in dogs treated with norepinephrine when compared with epinephrine and vasopressin. Similarly, Bellomo et al. (1999) demonstrated in normal and endotoxemic dogs that norepinephrine infusion increased renal blood flow even in the presence of systemic vasoconstriction, suggesting a possible beneficial effect of norepinephrine on renal perfusion in states of endotoxemic shock. In veterinary medicine, its use has been widely described in patients with sepsis, distributive shock, and states of refractory hypotension (Hopper; Epstein, 2012; Murphy; Rishniw; Silverstein, 2022).

Despite its recognized therapeutic efficacy, norepinephrine is not free from adverse effects. Accidental extravasation during intravenous administration may result in intense vasoconstriction at the affected site, leading to ischemia, tissue necrosis, and, in severe cases, deep structural compromise (Stefanos et al., 2023; Reynolds et al., 2014). For this reason, guidelines recommend administration through a central venous catheter whenever possible (Dellinger et al., 2013; Evans et al., 2021). However, in emergency situations, the use of peripheral venous access is frequent, especially in unstable patients in whom the time required to obtain central access may be critical.

Recent evidence suggests that peripheral administration of norepinephrine, when performed for a short period, through large-caliber veins, and under strict monitoring, may be considered relatively safe, without a significant increase in the rate of local complications (Delaney et al., 2020; Loubani; Green, 2015). Even so, cases of extravasation progressing to severe necrosis continue to be reported, reinforcing the need for constant surveillance and effective therapeutic strategies for the management of these injuries.

In this context, the treatment of necrosis induced by vasopressor extravasation requires approaches that promote tissue regeneration, modulation of the inflammatory response, and restoration of local perfusion. The present study describes the case of a female dog that developed extensive necrosis in the pelvic limbs after peripheral norepinephrine extravasation, progressing with a structural complication, and treated using a multimodal approach that included ozone therapy, laser therapy, and advanced dressings with Curatec technology.

An adult mixed-breed female dog approximately 4 years old and weighing 5.6 kg, previously submitted to ovariosalpingohysterectomy, was admitted on September 19, 2025, to a private veterinary clinic in Brazil, presenting with hypoactivity, anorexia, and arterial hypotension.

Upon admission, clinical evaluation revealed mildly pale mucous membranes, dehydration estimated at approximately 7%, systolic arterial pressure (SAP) of 90 mmHg, heart rate of 112 beats per minute, respiratory rate of 18 breaths per minute, and body temperature of 38.3 °C. Capillary blood glucose was severely reduced (25 mg/dL). Laboratory tests showed azotemia, with increased serum urea and creatinine, compatible with acute kidney injury, presumably secondary to sepsis associated with prolonged hypotension. Abdominal ultrasonography identified pyometra of the uterine stump, supporting the diagnosis of reproductive-origin sepsis, a condition frequently associated with hemodynamic instability and multiple organ dysfunction (Silverstein; Hopper, 2015).

During the first hours of hospitalization, the patient underwent serial clinical monitoring, including continuous assessment of systolic arterial pressure, body temperature, and blood glucose, which are fundamental parameters in the management of critically ill septic patients. At 10:00 a.m., the SAP was 90 mmHg, body temperature was 38.3 °C, and blood glucose was 25 mg/dL. At 12:00 p.m., SAP remained at 90 mmHg, with a reduction in temperature to 37.4 °C and transient normalization of blood glucose (90 mg/dL) after therapeutic interventions. However, at 2:00 p.m., a new decrease in SAP to 80 mmHg was observed, associated with recurrence of hypoglycemia (33 mg/dL), requiring intensification of vasoactive support. At 6:00 p.m., after therapeutic adjustments, the patient presented SAP of 90 mmHg, temperature of 37.8 °C, and blood glucose of 62 mg/dL, indicating partial hemodynamic stabilization.

Initially, fluid resuscitation with crystalloids was instituted at a rate of 10 mL/kg/h. However, due to the absence of a satisfactory hemodynamic response, vasoactive support with norepinephrine was initiated, administered through a peripheral intravenous route at a dose of 0.5 µg/kg/min, as recommended for distributive shock refractory to fluid therapy (Dellinger et al., 2013; Singer et al., 2016; Murphy; Rishniw; Silverstein, 2022). The first peripheral venous access was established in the left pelvic limb on the day of admission (09/19/2025), remaining until 09/20/2025. Subsequently, the access was changed to the right pelvic limb, where it remained until 09/22/2025, during which norepinephrine was continuously administered at the same dosage. Although central venous access is recommended, peripheral use is frequently employed in emergency contexts, provided that strict monitoring and limited duration are ensured (Dellinger et al., 2013; Delaney et al., 2020).

Supportive treatment included continuous fluid therapy, broad-spectrum antibiotic therapy, analgesia with dipyrone, administration of dexamethasone, vitamin B complex, antiemetics, and serial correction of hypoglycemia, in accordance with guidelines for the management of critically ill septic patients in veterinary medicine (Silverstein; Hopper, 2015; Hopper; Epstein, 2012).

From September 29, 2025, onward, the patient began to show intense pain in the pelvic limbs, associated with progression of local changes, including edema, skin color changes, and subsequent development of necrotic areas. Figure 1 illustrates the initial appearance of the pelvic limbs, showing the onset of the necrotic process. Initially, the musculoskeletal condition was attributed to the systemic repercussions of sepsis and prolonged hypotension. However, the clinical evolution and anatomical distribution of the lesions allowed correlation of the ischemic manifestations with the regions previously used for peripheral venous access, characterizing tissue necrosis secondary to norepinephrine extravasation. Vasopressor extravasation is recognized as a cause of intense local vasoconstriction, hypoperfusion, and progressive soft tissue necrosis, which may progress to deep and structural compromise when not identified early (Loubani; Green, 2015; Stefanos et al., 2023).

Figure 1: Right pelvic limb at the onset of the necrotic condition, showing edema, skin color alteration, and initial areas of ischemia compatible with tissue necrosis secondary to peripheral norepinephrine extravasation.

Due to the unfavorable clinical evolution, progression of cutaneous necrosis was observed, with blackening of the skin, formation of granulation tissue, and exposure of deep structures, including bones and tendons. These changes are shown in Figure 2, which demonstrates the extent and severity of the ischemic injury in the right pelvic limb. A multimodal therapeutic approach was then instituted, focusing on inflammatory modulation, stimulation of local perfusion, and tissue regeneration. Management included gradual and careful debridement of necrotic tissue, respecting the patient’s tolerance limits, with the objective of removing devitalized tissue, reducing the local inflammatory burden, and preserving adjacent viable tissue, as recommended in the treatment of complex wounds (Atiyeh; Hayek; Gunn, 2005; Wu et al., 2017).

Figure 2: Evolution of the lesion in the right pelvic limb, with cutaneous blackening, formation of granulation tissue, and exposure of deep structures, including bones and tendons, characterizing extensive soft tissue necrosis.

In parallel, six ozone therapy sessions were performed, used for their antimicrobial properties, modulation of the inflammatory response, and potential effect on tissue oxygenation, as described in the management of ischemic wounds and extensive necrosis (Bocci et al., 2011; Valacchi et al., 2018). The application of ozone therapy is presented in Figure 3. In association, three low-level laser therapy sessions were performed, used for their analgesic, anti-inflammatory, and biostimulatory effects, promoting angiogenesis, fibroblast proliferation, and increased collagen deposition, mechanisms widely described in tissue repair (Enwemeka et al., 2004; Posten et al., 2005; Ribeiro et al., 2022). Figure 4 shows the application of laser therapy during the patient’s treatment, demonstrating its integration into the management of the lesions.

Figure 3: Application of ozone therapy as part of the multimodal therapeutic approach, used with the objective of modulating the inflammatory response, favoring tissue oxygenation, and assisting in microbiological control of the wound.

Figure 4: Application of low-level laser therapy during the treatment of ischemic lesions, used for its analgesic, anti-inflammatory, and biostimulatory effects on the tissue repair process.

Local wound management included a structured protocol of advanced dressings with Curatec® products. In areas of active necrosis, gel containing polyhexamethylene biguanide (PHMB) was used, aiming at microbiological control, biofilm reduction, and facilitation of chemical debridement. In the already debrided regions, Curatec® AGE 30 Rayon was used, with the objective of maintaining a controlled moist environment, absorbing exudate, and favoring the formation of viable granulation tissue (Atiyeh; Hayek; Gunn, 2005; Wu et al., 2017). Initially, dressings were changed daily; after approximately 10 days, due to favorable clinical evolution, the interval was extended to 48 hours.

On October 15, 2025, favorable clinical evolution was observed, characterized by reduction of the necrotic areas, increase in viable granulation tissue, and beginning of tissue reorganization. Figures 5A and 5B illustrate the appearance of the pelvic limbs at this stage of recovery.

                                                                                                                       Figure 5A                                               Figure 5B

Figures 5A and 5B: Appearance of the right and left pelvic limbs on October 15, 2025, demonstrating favorable clinical evolution, with reduction of necrotic areas, increase in viable granulation tissue, and beginning of tissue reorganization.

On October 29, 2025, during an evening walk, a complete fracture of the right metatarsal bones occurred, accompanied by detachment of necrotic segments, characterizing a pathological fracture secondary to prolonged ischemia. The fracture is documented in Figure 6, which demonstrates the structural compromise of the limb. Pathological fractures associated with ischemic necrosis represent serious complications resulting from prolonged vascular injuries (Reynolds et al., 2014). After the event, the previously instituted therapeutic protocol was fully maintained, with limb stabilization, analgesia, and continuity of local care. The post-fracture evolution is presented in Figure 7, corresponding to November 1, 2025, and in Figure 8, referring to the follow-up performed on November 16, 2025, demonstrating progressive tissue recovery.

Figure 6: Complete pathological fracture of the right metatarsal bones that occurred on October 29, 2025, associated with deep ischemic necrosis and structural compromise of the adjacent tissues.

Figure 7: Appearance of the right pelvic limb on November 1, 2025, after fracture stabilization and maintenance of the multimodal therapeutic protocol, showing progression of the healing process.

Figure 8: Late evolution of the right pelvic limb on November 16, 2025, demonstrating progressive tissue recovery after the pathological fracture, with maintenance of granulation tissue and improvement in the local clinical appearance.

The patient was clinically discharged on November 13, 2025, remaining under home follow-up, with dressings performed every 72 hours. However, on November 23, 2025, she presented recurrence of purulent vulvar discharge, associated with inappetence and apathy, compatible with reactivation of the residual uterine infectious process. Considering the absence of clinical conditions for the definitive surgical procedure (removal of the uterine stump), reintroduction of antibiotic therapy was chosen. Despite the measures instituted, the condition evolved unfavorably, culminating in the patient’s death at home on December 9, 2025.

Vasopressor extravasation during peripheral intravenous infusion is a potentially severe iatrogenic complication, widely described in the medical and intensive care literature, and is associated with injuries ranging from mild cutaneous changes to extensive necrosis of soft tissues and deep structures. Norepinephrine, an essential drug in the management of distributive shock and refractory hypotension, has potent alpha-adrenergic activity and is recognized as one of the vasopressors with the greatest injurious potential when extravasation occurs (Loubani; Green, 2015; Reynolds et al., 2019).

The pathophysiology of vasopressor extravasation injury involves intense and sustained vasoconstriction of the local microcirculation, resulting in hypoperfusion, tissue hypoxia, and progressive necrosis. Additionally, increased intravascular hydrostatic pressure favors dissemination of the drug into the interstitial space, amplifying ischemic damage (Gault, 1993; Hadaway, 2017). Studies describe that the severity of the injury is directly related to the concentration of the vasoactive agent, duration of infusion, caliber of the vessel used, and early identification of extravasation (Reynolds et al., 2019; Lewis et al., 2014).

Although peripheral administration of vasopressors is considered acceptable in emergency situations, especially when central venous access is not readily available, systematic reviews demonstrate that, despite the low overall incidence of extravasation (2-4%), severe complications may occur and are underreported (Cardenas-Garcia et al., 2015; Tian et al., 2020). International guidelines recommend that, whenever prolonged vasopressor use is necessary, placement of central venous access should be prioritized, reducing the risk of tissue necrosis (Evans et al., 2021).

In the present case, progression to extensive necrosis and subsequent pathological fracture of the metatarsal bones reflects deep and prolonged ischemic compromise, compatible with previous reports of severe injuries caused by norepinephrine extravasation in humans (Loubani; Green, 2015; Reynolds et al., 2019). Although most reports describe cutaneous and subcutaneous involvement, there are descriptions of muscle, tendon, and bone involvement, especially when diagnosis and intervention do not occur immediately (Gault, 1993; Schummer et al., 2005).

Management of extravasation injuries remains a clinical challenge, as there are no randomized clinical trials defining a standard therapeutic protocol. However, there is consensus regarding the need for immediate interruption of the infusion, catheter removal, adequate analgesia, strict monitoring, and a local approach directed at reversal of ischemia and preservation of viable tissue (Hadaway, 2017; Reynolds et al., 2019). Local infiltration of phentolamine is considered the pharmacological treatment of choice for vasopressor extravasation, as it antagonizes alpha-adrenergic receptors and restores local perfusion, although its availability is limited in several clinical and veterinary contexts (Loubani; Green, 2015; Lewis et al., 2014).

In the absence of specific antidotes, adjuvant strategies have been described with the objective of modulating the inflammatory response, favoring tissue oxygenation, and stimulating repair. Ozone therapy has been associated with improvement in local perfusion, antimicrobial action, and modulation of oxidative stress, showing promising results in the management of ischemic and chronic wounds, although high-level evidence is still lacking (Bocci et al., 2011; Valacchi et al., 2018). Similarly, low-level laser therapy has been widely studied as an adjuvant tool in the treatment of complex wounds, demonstrating positive effects on analgesia, angiogenesis, fibroblast proliferation, and collagen synthesis (Enwemeka et al., 2004; Hopkins et al., 2004).

The use of advanced dressings and structured protocols for local care is widely recommended in the literature on complex wound treatment. Maintenance of a controlled moist environment, associated with microbiological control and progressive debridement, favors the formation of granulation tissue and reduces the risk of secondary infection (Falanga, 2005; Jones et al., 2018). In the present case, such strategies initially allowed stabilization of the lesion and favorable evolution of the wound bed, even after the pathological fracture occurred.

Despite the initially satisfactory local response, the subsequent unfavorable clinical evolution demonstrates that critically ill patients, especially those submitted to prolonged vasoactive support, remain susceptible to severe systemic complications. This outcome reinforces the importance of rigorous prevention protocols, continuous monitoring of venous access sites, and early decision-making regarding conversion to central access in patients receiving vasopressors (Cardenas-Garcia et al., 2015; Evans et al., 2021).

Thus, this report contributes to the literature by documenting a rare and severe complication of norepinephrine extravasation in veterinary medicine, highlighting the need for constant surveillance, early diagnosis, and a multimodal therapeutic approach based on the pathophysiology of the injury and the best available evidence, although predominantly derived from the human literature.

This report documents a severe complication associated with peripheral norepinephrine extravasation in a critically ill female dog, resulting in extensive tissue necrosis and pathological fracture secondary to prolonged ischemia. Although norepinephrine remains the first-choice vasopressor in the management of septic shock refractory to fluid resuscitation, the findings presented reinforce that its peripheral administration, even when clinically indicated and widely used in emergency settings, carries an inherent risk of highly morbid local ischemic injuries.

The clinical evolution observed demonstrates that initial manifestations, such as disproportionate localized pain, may precede evident cutaneous changes and should be interpreted as warning signs of possible vasopressor extravasation. Therefore, strict monitoring of the infusion site, limitation of the duration of peripheral use, and prompt transition to central venous access, when feasible, are fundamental measures for mitigating complications.

The multimodal therapeutic strategy adopted, combining progressive debridement, ozone therapy, low-level laser therapy, and advanced dressings, contributed to modulation of the inflammatory response, stimulation of tissue repair, and control of lesion progression, even in the presence of deep compromise of the affected structures. Although the clinical results observed are encouraging, extrapolation of this approach should be performed with caution, since the available evidence for these adjuvant therapies in vasopressor-induced necrosis remains limited.

Overall, this case adds relevant clinical evidence to the veterinary literature on vasopressor extravasation, emphasizing the need for standardized protocols for prevention, early detection, and management of associated injuries. Prospective studies are necessary to define ideal therapeutic strategies and establish evidence-based recommendations for the treatment of vasopressor-induced necrosis in critically ill veterinary patients.