Recreational drug use, mainly through intravenous (IV) administration, poses a significant global health challenge, leading to both systemic and local vascular complications. While systemic issues such as infections and overdoses are well-documented, severe local vascular damage caused by IV drug use remains underreported despite its potential for severe outcomes. Intra-arterial drug injection (IADI), a familiar yet often unintentional phenomenon first described by Van Der Post in 1942, can lead to life and limb-threatening conditions such as acute ischemia, gangrene, pseudoaneurysms, rhabdomyolysis, and compartment syndrome [1, 2]. These complications, if not promptly identified and treated, may result in irreversible tissue loss, amputation, or death. Due to the complex pathogenesis and variety of injected substances, there are no universal evidence-based guidelines regarding the management of inadvertent IADI ^[3]. Current management strategies prevent further vascular compromise and restore blood flow. Early interventions, including anticoagulation, vasodilation, thrombolysis, hyperbaric oxygen therapy, and embolectomy, can help prevent tissue necrosis ^[2]. In a case study involving IADI, a multi-drug regimen of anticoagulants, vasodilators, and thrombolytic agents effectively resolved ischemic effects, while fasciotomy contributed to successful limb salvage ^[4]. However, the effectiveness of these interventions is highly reliant on timely diagnosis and rapid treatment. When medical consultation is delayed, and necrosis and gangrene have already set in, surgical intervention, such as excision of necrotic tissue or amputation, is often the only viable treatment option ^[5]. A study evaluated 48 patients over 17 years, all receiving the same treatment protocol, and found that 12 of the 13 patients who developed tissue necrosis ultimately required amputation ^[6]. In this retrospective case series, we present five patients who reported at a tertiary care hospital with upper limb gangrene following repetitive IV drug use. These cases underscore the severe vascular complications that can arise from IV drug use, particularly when there is delayed medical intervention. By detailing the clinical presentations, management strategies, and outcomes of these cases, we aim to increase awareness among healthcare providers about the risks of IV drug use and highlight the necessity of early diagnosis and intervention to prevent irreversible tissue loss.

Case 1: 29-year-old male with left-hand gangrene

Presentation

A 29-year-old male presented with a 30-day history of progressive blackening and pain in his left hand, fingers and palm. He reported repetitive IV use of heroin and methadone over 2 years, with injection sites around the left wrist, forearm, and elbow. The patient was human immunodeficiency virus (HIV) and hepatitis C virus (HCV) positive, with no significant family history of vascular or genetic disorders. On physical examination, dry necrosis extended from the fingers to the wrist joint, with no detectable distal pulses. Clinical findings suggested vascular occlusion at the distal forearm level.

Investigations

Imaging studies were not performed due to the patient’s financial constraints.

Intervention

A below-elbow amputation was performed based on clinical judgment. Postoperatively, the patient received IV antibiotics for 5 days.

Outcome

The patient was discharged in stable condition but did not attend follow-up visits.

Case 2: 23-year-old male with right-hand gangrene

Presentation

A 23-year-old male presented with a 15-day history of worsening pain and discoloration in his right hand, progressing to dry gangrene. He reported a history of oral buprenorphine use that transitioned to IV use 1.5 months prior. Injection sites were primarily on both forearms near the elbow, with greater involvement on the right side. On examination, dry gangrene extended from the fingertips to the metacarpophalangeal (MCP) joints, with cyanosis and mottling up to the mid-forearm.

Investigations

Doppler ultrasonography (USG) and computed tomography (CT) angiography confirmed significant vascular compromise, including ulnar artery thrombosis and radial artery stenosis, contributing to distal blood flow loss.

Intervention

A below-elbow amputation was performed. Postoperatively, the patient received IV antibiotics for 5 days.

Outcome

The patient was discharged in stable condition but did not return for follow-up.

Case 3: 21-year-old male with right-hand gangrene

Presentation

A 21-year-old male presented with a 10-day history of blackened fingers and palm of his right hand following repetitive IV use of heroin, buprenorphine, methadone, and butorphanol over 1 year. The patient had no known infections such as HIV or HCV. On examination, dry gangrene involved the MCP joints of the index finger and the proximal interphalangeal (PIP) joints of the thumb, middle, and little fingers, with discoloration over the dorsum of the hand.

Investigations

Doppler USG revealed thrombophlebitis of the cephalic vein without significant arterial involvement. CT angiography was not performed due to financial constraints.

Intervention

Partial amputation of the gangrenous fingers was performed, including nibbling and closure at the PIP joint of the thumb, middle, and little fingers, and the MCP joint of the index finger. Postoperative care included IV antibiotics for 5 days.

Outcome

The patient recovered well post-surgery but did not attend follow-up visits.

Case 4: 27-year-old male with recurrent finger gangrene

Presentation

A 27-year-old male presented with a 15-day history of progressive blackening of the right index and middle fingers, extending to the MCP joint. He reported repetitive IV drug use for 5 years, including fentanyl. Three months prior, he underwent amputation of the little finger at the PIP joint following gangrene. On examination, dry gangrene affected the index and middle fingers, with skin changes on the palmar aspect of the hand.

Investigations

USG A-V Doppler was recommended, but the patient declined imaging studies.

Intervention

Ray amputation was performed. Postoperatively, the patient received IV antibiotics for 5 days.

Outcome

The patient was discharged in stable condition but did not return for follow-up visits.

Case 5: 22-year-old male with early-stage gangrene

Presentation

A 30-year-old male presented with a 10–12-day history of blackening of the fingertips and thumb of his right hand. He admitted to repetitive IV drug use over six months, primarily injecting buprenorphine near the right wrist. The patient was HCV and HIV positive. On examination, dry necrosis was limited to the tips of the fingers, thumb, and palm and dosrsum of the right hand.

Investigations

CT angiography was done, and it showed blockage of the Ulnar artery at its origin.

Intervention

Below elbow amputation was done at the level of the mif forearm.

Outcome

The patient was discharged in good condition and loose to follow-up.

Summary of key findings

In Case 1, the patient’s refusal of Doppler imaging and CT angiography due to financial limitations complicated the assessment of vascular compromise and may have delayed optimal intervention. Similarly, CT angiography could not be performed in Case 3. All patients were discharged in stable condition following surgery. However, the lack of follow-up made it impossible to fully assess the long-term success of the interventions and potential complications, including infection or further disease progression as shown in Table 1.

Inadvertent IADI is a well-documented complication, especially in long-term addicts with sclerosed superficial veins. Such injections can lead to vasospasm, thrombosis, ischemia, compartment syndrome, and eventually gangrene. This case series highlights the vascular complications arising from IV drug use, particularly when medical intervention is delayed. All five patients presented with severe gangrene of the upper extremities, necessitating surgical intervention in the form of partial or complete limb amputations. Literature indicates that the average amputation rate among patients experiencing ischemic complications following IADI is 29% ^[7]. Consistent with previous studies, the amputation rate in this case series was significant.

Pathogenesis of vascular injury

The vascular complications associated with IADI are multifactorial. Direct endothelial damage occurs due to the chemical properties of the injected substances and their metabolites. This is compounded by secondary effects, such as:

• Vasospasm: Triggered by irritants in the drug formulation
• Toxic vasculitis: Caused by contaminants or additives
• Thrombosis: Resulting from mechanical trauma and chemical irritation, leading to arterial obstruction and tissue ischemia.

Studies indicate that unintentional intra-arterial injection leads to a cascade of ischemic events characterized by vasospasm, inflammation, and thrombosis, ultimately resulting in irreversible tissue necrosis if not treated promptly ^[7].

Management strategies in literature

The management of ischemic complications from IV drug use, particularly intra-arterial injections, requires rapid intervention to restore blood flow and prevent tissue necrosis. Following an intensive treatment protocol combining vasodilators, anticoagulants, antibiotics, steroids, and thrombolysis, 13 out of 16 patients developing limb ischemia had normal extremities with no morphological or functional alterations ^[8]. Ipaktchi et al. also reported successful thrombolytic management of an ischemic hand 18 h after an accidental intra-arterial injection into the ulnar artery ^[3]. IADI patients who received treatment within 24 h after injection have significantly better outcomes, while delays in treatment lead to higher rates of amputation [6, 8-10]. Unfortunately, these patients often hide their history of drug abuse and delay seeking medical attention ^[5]. The damage is frequently advanced when they present to healthcare services. The rapid progression of gangrene in the patients included in this case series underscores the need for early intervention to prevent irreversible damage. In these cases, the opportunity to restore blood flow and avoid tissue death was likely missed due to late presentation and extensive tissue damage.

Case series findings and comparison with literature

This case series emphasizes the critical need for early recognition and management of IV drug-induced ischemia to prevent irreversible damage. Healthcare providers should be vigilant in identifying early signs of vascular compromise, even when symptoms appear mild. Prompt imaging, such as Doppler USG or CT angiography, can provide diagnostic and therapeutic benefits by assessing disease progression and aiding in prognosis [3, 5]. This study is limited by its small sample size. In addition, the absence of follow-up in these cases is a significant limitation, preventing the assessment of long-term outcomes, including infection risk, stump healing, and overall limb function. This highlights broader socioeconomic factors that played a significant role in the delayed presentation, refusal of diagnostic evaluations, and lack of follow-up common issues in managing IV drug users. Future studies should explore structured follow-up programs and outreach efforts to ensure that IV drug users receive the care they need to prevent catastrophic outcomes such as limb amputation.

Challenges in the management of IV drug users

This study highlighted several challenges in the management of IV drug users:

1. Delayed presentation: Patients often conceal their drug abuse history, leading to delays in seeking medical care until complications are severe
2. Limited diagnostic resources: Financial and logistical barriers frequently hinder access to imaging and advanced interventions
3. Lack of follow-up: None of the patients in this series returned for postoperative follow-up, reflecting a significant gap in continuity of care.

These challenges emphasize the need for tailored healthcare approaches, including early outreach, patient education on the risks of IV drug use, and structured follow-up programs to mitigate long-term complications.

Other causes of dry gangrene

1. Diabetic vasculopathy
2. Peripheral arterial disease
3. Buerger’s disease
4. Cellulitis
5. Trauma
6. Raynaud’s disease.

Inadvertent intra-arterial injection in IV drug users can result in severe complications such as ischemia, gangrene, and the need for amputation. While surgical intervention is often necessary when catastrophic complications develop, early recognition and medical treatment – including anticoagulants, vasodilators, and thrombolytic therapy – may improve outcomes and prevent tissue damage and limb loss. This case series serves as a reminder of the critical importance of early diagnosis and intervention in these cases to reduce the likelihood of severe adverse sequelae.

Diagnostic Criteria for early diagnosis to prevent gangrenous changes

1. Clinical symptoms: Numbness, pain, swelling, discoloration, breaks in the skin, cold peripheries, discharge
2. Clinical signs: Delayed or absent capillary refill, reduced or absent distal pulses
3. Clinical test: Allen test to check patency of radial and ulnar arteries.
4. The patient is asked to clench both fists tightly for 1 min at the same
5. Pressure is applied over the radial and ulnar arteries simultaneously so as to occlude
6. The patient then opens the fingers of both hands rapidly, and the examiner compares the colour of The initial pallor should be replaced quickly by rubor.
7. The test may be repeated, this time occluding the ulnar arteries.
8. Imaging test:
   1. USG color Doppler (arteriovenous)
   2. CT scan (angiography).

This case series highlights the importance of early detection and intervention in managing vascular complications resulting from IV drug abuse. Although severe complications, including gangrene and amputation, were necessary outcomes in these cases, timely medical management such as vasodilators and thrombolytics could prevent irreversible tissue loss and improve the prognosis. The report underscores the need for healthcare providers to remain vigilant in diagnosing and managing ischemic conditions in drug users to avoid catastrophic outcomes.