Upper Limb Wound Profile in Patients Who Inject Heroin and Fentanyl Mixed With Xylazine

Abstract

Background:

Over the last few decades, hand surgeons have described a variety of wounds resulting from opioid use disorder (OUD). In the Philadelphia region, fentanyl mixed with xylazine has risen as a substance of choice. Our primary focus is to report and compare the upper limb wound morphology in patients using fentanyl/xylazine with patients using heroin.

Methods:

A retrospective cohort study was performed by reviewing charts of patients seen in consultation in a single plastic surgeon’s private practice for upper limb soft tissue infections associated with opioid use from September 1, 2019, to November 30, 2023. Seventy patients were included and stratified based on wound morphology.

Results:

We identified 70 patients (36% male, 64% female). In the heroin group, the most common wound was abscess (50%). In the fentanyl/xylazine group, it was full-thickness wound (55%). Chi-square analysis revealed a significant relationship between substance used (heroin or fentanyl/xylazine) and wound severity (mild/moderate or severe), χ² (1, N = 70) = 42.06, P < .0001.

Conclusions:

There is a paucity of medical literature about the spectrum of wound manifestations in OUD. Our data suggests that heroin use more commonly causes unilateral soft tissue injuries, which is likely a result of site-specific infection with intravenous administration. Patients using fentanyl/xylazine had a higher rate of bilateral upper limb injury and presented with more severe wounds than patients who used heroin. Hand surgeons must be informed on the spectrum of wound morphology with OUD and nuances between substances to best manage them in their practice.

Introduction

Hand and upper extremity infections constitute a large portion of surgical injuries with the potential to cause functional impairment and reductions in quality of life. ¹ The sequelae of infection, spread, amputation, and potentially death can pose challenges for surgeons in patients using intravenous drugs. ¹ In many surgical disciplines, time is tissue, and hand injuries are no different. As such, surgeons must recognize the spectrum of wound morphology in patients with substance misuse.

Upper extremity injuries linked to intra-venous drug use (IVDU) present many challenges to surgeons. There is a high risk of polymicrobial infections, poor health state, and long-term comorbidities following treatment of injuries. ¹ There is a wide scope of skin and soft tissue infections that intravenous drug using patients can present with such as abscesses, cellulitis, and complex gangrenous infections. ¹ The scope of management is equally as vast, including conservative management, antibiotics, incision and drainage, and amputation in severe cases. ¹ When faced with such a large spectrum of management, adequate information regarding xylazine, heroin, and fentanyl-related skin infections, as in this review, are essential.

Xylazine, a veterinary sedative and a2 receptor agonist, has been increasingly found as an illicit drug “cutting agent” contributing to neurologic depressive effects at the expense of purity.^2,3 It is used in combination with fentanyl as it potentiates its effects in users. Xylazine use has been associated with chronic wounds with increased risk of necrosis. ³ These wounds, upon presentation, are usually extensive and escalate in severity over a short period, seemingly irrespective of the patient risk behaviors or scope of substance abuse, mild or severe. ² There are a few reports of soft tissue injuries on the face. It is not approved for human use and has been linked to an increase in overdose deaths. ³ Xylazine use can also cause skin ulcers, abscesses, lesions, drowsiness, amnesia, hypotension, bradycardia, and bradypnea in patients. ³ In addition to the aforementioned symptoms, patients using xylazine have increasingly prevalent overdose deaths. ⁴ Furthermore, patients using xylazine are more likely to inject, which leads to more severe symptoms and comorbidities. ⁵ These patients are also more likely to have social determinants of health that result in barriers to care. ⁵

The highest usage rates of xylazine-containing opioids can be found in Philadelphia, Pennsylvania. ⁶ From 2010 to 2015, xylazine-related overdoses increased in prevalence from 2% to 31%, which was a considerable expansion for the limited time frame. ² The research is comparatively limited on soft tissue and skin infections (SSTI) caused by xylazine when compared with those on heroin and fentanyl. ² There are a few reports of xylazine soft tissue infections presenting on the face and neck, as Oneil and Kovach present in “Xylazine Associated Skin Injury” in a 32-year-old man who injected fentanyl laced with xylazine into his arms and neck. Most patients, however, present with upper or lower extremity injuries. This case study compares wound morphologies of SSTI associated with fentanyl/xylazine and heroin in patients in Pennsylvania being treated by a plastic surgeon.

Materials and Methods

This retrospective cohort study describes patients managed by a single plastic surgeon in their private practice. Inclusion criteria were individuals admitted with upper limb soft tissue infections related to heroin or fentanyl mixed with xylazine use between September 1, 2019, and November 30, 2023, and seen in consult by the plastic surgeon. The latter experienced eight 24-hour hand call shifts per month for the local level 1 trauma center over the 4 years, which represents 25% of hand call coverage at this institution. Patients were separated into 2 groups based on substance used. We recorded patient age, date of consult, sex, diagnosis and limb of interest regarding soft tissue injury, and subsequent operative interventions if any. Soft tissue wounds were subsequently classified as mild/moderate (cellulitis, abscess) or severe (partial-thickness wound, full-thickness wound, full-thickness wound with osteomyelitis, full-thickness wound with exposed bone and gangrene). Chi-square analysis was performed to assess the relationship between substance of use and wound severity. All analyses were performed using SAS version 9.4.

Results

Seventy patients (64% female and 36% male) with upper extremity injuries related to opioid use were identified. In-depth demographic information was difficult to obtain due to the high incidence of noncompliance in this patient population. Thirty patients self-admitted to heroin use and 40 to fentanyl/xylazine use. Table 1 demonstrates that more patients in the fentanyl/xylazine group presented with severe wounds (N = 26), compared with the heroin group (N = 3). Chi-square analysis revealed a significant correlation between substance used and wound severity, χ²(1, N = 70) = 39.53, P < .001.

Table 1.

Degree of Wound Severity Based on Reported Substance Use (P < .001).

Substance used	Degree of wound severity
	Mild/moderate n (%) a	Severe n (%)	Total n (%)
Heroin	27 (38.6)	3 (4.3)	30 (42.9)
Fentanyl/xylazine	14 (20.0)	26 (37.1)	40 (57.1)
Total	40 (57.1)	30 (42.9)	70 (100.0)

^an = number of patients; % = percentage of that group.

The trend in higher rates of wound severity in the patients admitting to fentanyl/xylazine use can be further characterized by looking at wound subtypes. In Table 2, it is shown that within the heroin group, abscess and cellulitis were the most common presentations, while there were no patients with wounds beyond full-thickness wound with osteomyelitis. In patients who used fentanyl/xylazine, the most common wounds were full-thickness wound and abscess (Figure 1). In addition, 12 patients using fentanyl/xylazine had sequelae beyond full-thickness wounds including osteomyelitis, exposed bone, and gangrene (Figure 2).

Table 2.

Wound Profiles in Fentanyl/Xylazine and Heroin Groups.

Wound type	Fentanyl/xylazine n a (% of column)	Heroin, n (% of column)
Cellulitis	3 (7.5)	12 (40.0)
Abscess	10 (25.0)	15 (50.0)
Partial-thickness wound	1 (2.5)	0 (0.0)
FTW	14 (35.0)	2 (6.7)
FTW with osteomyelitis	4 (10.0)	1 (3.3)
FTW with exposed bone	6 (15.0)	0 (0.0)
Gangrene	2 (5.0)	0 (0.0)
Total	40 (100)	30 (100.0)

FTW = full-thickness wound.

^an = number of patients; % = percentage of that group.

Figure 1.

Abscess on right hand dorsum from heroin use.

Figure 2.

Distal gangrene of right hand (left) and full-thickness wound of right hand (right), both from fentanyl/xylazine.

Overall, left arm wounds (N = 38) were most prevalent. Wound severity and laterality was analyzed in both groups. For the fentanyl/xylazine group, these variants were found to be statistically significant with Fisher exact test (Table 3). Five of the 6 patients with bilateral wounds in the fentanyl/xylazine group were classified as having severe wounds. In the fentanyl/xylazine group, patients with left arm and bilateral wounds had higher incidences of severe wounds. Wound location and severity were not found to be correlated in the heroin cohort (Table 4).

Table 3.

Wound Severity Based on Arm for the Fentanyl/Xylazine Group (P = .0229).

Wound side	Wound severity
	Mild/moderate n (%) a	Severe n (%)	Total n (%)
Bilateral	1 (2.5)	5 (12.5)	6 (15.0)
Left arm	4 (10.0)	12 (30.0)	16 (40.0)
Right arm	9 (22.5)	9 (22.5)	18 (45.0)
Total	14 (35.0)	26 (65.0)	40 (100.0)

^an = number of patients; % = percentage of that group.

Table 4.

Wound Severity Based on Arm for the Heroin Group (P = .7831).

Wound side	Wound severity
	Mild/moderate n (%) a	Severe n (%)	Total n (%)
Left arm	20 (66.7)	2 (6.7)	22 (73.4)
Right arm	7 (23.3)	1 (3.3)	8 (26.6)
Total	27 (90.0)	3 (10.0)	30 (100.0)

^an = number of patients; % = percentage of that group.

In Table 5, the subsequent need for surgical intervention was observed for both groups. It was found, through χ² analysis, the incidence of this was higher in the fentanyl/xylazine group, χ²(1, N = 70) = 26.76, P < .001. All nonoperative patients were managed with local wound care. Of the 3 patients in the heroin group who were brought to the operating room, 2 received split-thickness skin grafts and 1 underwent right distal thumb amputation. Of the fentanyl/xylazine patients, 20 were brought to the operating room for surgical intervention. Interventions included debridement, split- and full-thickness skin grafts, extracellular matrix placement, various flaps, and amputations. Indeed, 3 patients underwent flaps including the radial forearm flap, and 10 required amputations, ranging from a partial digit to the entire forearm. All patients were lost to follow-up.

Table 5.

Intervention Based on Reported Substance Use (P < .001).

Substance used	Intervention
	Non-surgical n (%) a	Surgical n (%)	Total n (%)
Heroin	27 (38.6)	3 (4.3)	30 (42.9)
Fentanyl/xylazine	20 (28.6)	20 (28.6)	40 (57.1)
Total	47 (67.1)	23 (32.9)	70 (100.0)

^an = number of patients; % = percentage of that group.

Discussion

There has been a consistent increase in opioid use nationwide, resulting in hospitalizations, opioid-related deaths, and infections in the last decade. ¹ Fentanyl and xylazine have contributed significantly to this increase. According to the Centers for Disease Control and Prevention, fentanyl has been associated with over half of opioid-related hospitalizations and deaths in 10 states in 2016, nearly a decade ago. In addition, these hospitalizations constitute significant financial medical burden on the health care system and patients. ¹ San Francisco alone spends roughly 9.9 million annually on hospitalizations related to soft tissue infections, and of those about 70% are heroin users. ¹ Many of these patients are uninsured. Medicaid is the largest payer for IVDU-related hospitalizations annually.^1,7

The use of xylazine has also simultaneously increased in prevalence in opioid-related deaths and skin infections.^8,9 The scope of research on xylazine-associated skin infections is limited largely to case studies and is relatively new. In a sample of health care workers in Massachusetts, Maryland, Michigan, Minnesota, North Carolina, Pennsylvania, and Texas, participants provided insight on their own experiences with xylazine-associated wounds. ² These wounds are described commonly as small lesions that appear mostly on the extremities located at, and away from, the subcutaneous injection sites. ¹⁰ These lesions can be found hours or days after exposure, rapidly evolving into complex, large wounds. In worse cases, they result in amputation of the affected extremity.^2,11

In our study, we identified 70 patients with opioid injection-related upper extremity wounds. All patients were seen in consult by the plastic surgeon during each 24-hour call shift. We categorized wound depth as partial or full, with less severe wounds constituting full epidermis and partial dermis involvement and more severe wounds including all depths of skin. Of the 70 patients, we identified 30 patients who reported exclusive use of heroin, and 40 patients who reported use of fentanyl with xylazine. Within the heroin group, 4.3% of patients presented with severe wounds while 37.1% of patients in the fentanyl/xylazine group had severe wounds. We found this to be statistically significant and consistent with our hypothesis that fentanyl/xylazine wounds are more severe. The patients who injected heroin presented most commonly with abscesses or cellulitis, whereas patients who used xylazine had more complicated full-thickness wounds that included osteomyelitis or exposed bone. However, only one patient of all 30 within the heroin group presented with osteomyelitis.

Reciprocally, the patients within the fentanyl/xylazine group presented with fewer of the less severe wounds, with only 3 having cellulitis. Our results show that not only do fentanyl/xylazine users have more severe wounds, but they also possess less of the simpler wound morphologies. This finding is very important and integral to our findings because it reinforces the assertion that fentanyl/xylazine causes an increase in serious wounds and not simply because they cause more wounds in general. This is indicative of a poignant shift toward more severe complications. In addition to causing more severe wounds, injection of fentanyl/xylazine causes bilateral wounds at higher rates than that of heroin. Furthermore, patients with wounds attributed to fentanyl/xylazine experienced higher frequency of surgical interventions, whereas heroin users had more nonsurgical interventions.

The results of our study show that xylazine users had more severe wounds than heroin, require more surgical intervention, and are more likely to affect distal sites. In addition, heroin-related injuries tended to more often be abscesses and deep space infections that required emergent intervention while xylazine-related wounds tended to be more smoldering and chronic. Some properties of xylazine have led to theories that it has risk of vasoconstriction with injection. Due to the pervasive and extensive nature of xylazine wounds, it is evident that more research and studies are necessary to fully elucidate key components and properties of xylazine as it shapes the presentation of the current opioid crisis. A limitation of this study is the lack of in-depth demographic information on these patients, and any follow-up information, which is most likely a reflection of the socioeconomic challenges these patients face, and a contributor to poor health outcomes. Johnsen et al ¹² reported high incidences of homelessness, psychiatric diagnoses, high predilection for leaving the hospital against medical advice, and repeated drug use in patients with xylazine-related wounds. This study contributes to the growing knowledge on xylazine to inform plastic surgeons and physicians of the devastating sequelae of its use so they may be best equipped to treat patients who present with them.