Amputation After Intra-Arterial Injection of Crushed Morphine Tablets

A 51-year-old man presented to the hospital in severe pain approximately 1 hour after injecting three crushed morphine tablets (10 mg) into his right radial artery. Clinicians learned that he had been seeking relief due to an abstinence crisis. He had a history of alcoholism and was a regular user of illicit drugs.

He was admitted and treated with opioids, but his pain persisted without improvement. Ultimately, the patient required a brachial plexus blockade.

A physical examination upon admission found his right upper arm to be cold and cyanotic. Pulse in the brachial, axillary, radial, and ulnar arteries was palpable with preserved amplitude. Results of a Doppler ultrasound of the arteries in the affected limb were normal; however, the patient’s fingers were cold and cyanotic.

Clinicians obtained a thermal image of the right hand obtained using a Flir C3 portable thermal camera that had been configured to display a color palette.

This imaging (Figure) showed a progressive change from hot-to-cold in the right hand, as had been noted in clinical examination of the patient.

The group noted that use of the thermal imaging device “allowed a more precise assessment of the initial tactile observation that the fingers felt colder than they should be, suggesting perfusion problems in some regions of the right hand.”

The patient was started on full heparinization with enoxaparin (Lovenox), nitroglycerin, and alprostadil (prostaglandin E1), with corticosteroid treatment to help reduce the inflammatory response. Heat was applied to his entire upper right arm using orthopedic cotton.

However, clinicians noted increasing cyanosis affecting the patient’s right hand and significant swelling of the whole upper limb, indicating progression of compartment syndrome. At 23 hours post-admission, the patient received decompressive fasciotomy of the right forearm.

The patient was transferred to the ICU, where he developed rhabdomyolysis and kidney failure, which was managed with dialysis. The perfusion of his right arm and forearm gradually improved, but there was a critical worsening of perfusion affecting his right hand, with extensive necrosis.

On day 10 of admission, clinicians removed dead tissue that remained from a previous fasciotomy; the patient underwent debridement of both sides of his forearm and amputation of the distal phalanx of all five fingers.

Fourteen days after being admitted to hospital, the patient had recovered normal renal function and was discharged from the ICU. He received follow up care from the vascular and plastic surgery team.

Due to the significant progression of necrosis that had occurred in his hand, the patient later required surgery to remove proximal phalanges, followed by surgical reconstruction of the remnant of his right hand.

Discussion

Clinicians presenting this case of a man who developed severe complications after injecting crushed morphine tablets into the radial artery noted that infrared thermography can help inform the diagnosis and monitoring of acute arterial ischemia, as well as aid in the delimitation of the ischemic area.

Potential complications due to accidental or intentional injection of crushed tablets into the arteries are not well-documented, authors noted, and “no effective medical treatment against lesion progression has been reported to date.”

The group stressed that timely treatment from a specialized vascular team after such an injection can have a significant impact on outcomes. This was noted in a 2015 review that found an overall mean 29% incidence of amputation after inadvertent intra-arterial drug injection of the upper extremity, a risk that was significantly higher among patients presenting 14 hours or more after injection and for those injecting crushed pills rather than pure substances.

That the nature of the injected substance influences the risk and extent of potential complications was reiterated by the case authors, who noted that the odds of necrosis were particularly heightened in the case of injection of benzodiazepines compared with other drugs.

A 2019 review noted that “a number of drugs used in anesthetic practice (fentanyl, succinylcholine, pancuronium, atropine, rocuronium) have been injected intra-arterially without causing serious damage to vessels, while others (thiopental, diazepam) have caused significant morbidity.”

Complications are frequently more dependent on the excipients (and on impurities in pills acquired illegally) contained in a tablet than the active ingredient itself, case authors explained. Some excipients can have negative effects on blood flow and on the vascular endothelium. For instance, microcrystalline cellulose (MCC), the primary excipient in many medications taken orally, including morphine tablets, has the potential to cause or exacerbate lesions when injected into an artery, they wrote. The group cited a reported case of ischemia that developed after arterial injection of a crushed zolpidem tablet, which “highlighted the embolic potential as the predominant mechanism of injury effect of MCC.”

MCC is a frequently used excipient because of its low reactivity to a medication’s active constituents, case authors noted, along with other properties such as that “it is insoluble in water and most organic solvents, resistant to degradation in water, and water absorbent, resulting in lower particle agglomeration.” The group referred to a study in dogs that showed injection of pure codeine into the femoral arteries caused no harm, whereas the addition of MCC resulted in acute symptoms of ischemia and gangrene.

Case authors cited another report in which crushed tablets of illicit drugs thought to contain MCC were taken through a peripherally inserted central catheter, ultimately resulting in the death of a young patient. Case authors noted that the postmortem turned up “extensive pulmonary foreign body embolism involving small-to-medium-sized arteries with segmental intraluminal and occasional subsegmental involvement.” Although fatal cases of intravascular foreign body embolism have been reported, case authors noted that this generally develops over the course of years, as an increasing accumulation of MCC impairs pulmonary microcirculation. The group added that infusion of crushed tablets into an artery causes more harm than infusion into veins, and that distal sites are more likely to cause serious complications such as amputation.

The group observed that unintentional venous or arterial injection is rare; lack of data leaves its actual incidence unknown. One review suggested that most inadvertent arterial injections involve the brachial artery (40%) and the radial artery (24%). Deliberate and accidental injection of crushed tablets cause the same symptoms, which generally include both severe pain (78%) and cyanosis and spots (46%). About one-third of patients present with impaired motor function or sensory deficits; about one-quarter have reduced body temperature.

Authors explained that electromagnetic radiation in the thermal infrared range is measured by thermal imaging without use of ionizing radiation, making it a safe methodology that is increasingly used as a diagnostic tool in various areas of medical practice. These devices detect infrared radiation emitted from the body surface, allowing changes in skin temperature to be determined quickly, accurately, and without contact. In contrast to contact probes, imaging thermography does not affect the region where the temperature is measured, since it does not absorb heat from the skin.

Changes in skin temperature may be caused by a variety of factors, authors wrote, including increased metabolic activity in the muscles and increased or decreased blood perfusion in the region.

Because these temperature patterns often reflect changes in blood flow, infrared thermography has the potential to assess the extent of tissue perfusion in cases involving acute ischemia, they stated. Thermal cameras are usually set to color palette mode, with red indicating the hottest area and blue the coldest, so that imaging thermography also provides “a temperature map of a skin region, [and] the physician can obtain even richer information.”

In cases where “large vessels have normal flow, this flow does not reach a subset of small vessels, causing perfusion deficiencies,” they noted; theoretically, this means that thermography might be a more effective means of imaging than ultrasound-based techniques.

In the present case, the patient used a single injection of three morphine tablets, which authors noted represents a sizeable volume to inject in the distal portion of the radial artery, “with practically no time and blood volume for dilution; causing massive obliteration of the entire palmar arch of the right hand, ischemia, necrosis, and amputation.”

The group added that the thermal image revealed a large difference in temperature “between the proximal dorsal portion of the hand (in red) and the fingers (in blue), reinforcing that the flow measured on the arterial Doppler ultrasound, especially in the radial and ulnar arteries, was not, in this particular case, a good estimator for finger perfusion.”

Case authors wrote that without any means of removing MCC from microcirculation, “treatment of accidental or intentional injection of crushed tablets into the arterial circulation is still based on analgesia, vigorous hydration, corticotherapy, vasodilators, and anticoagulants and surgical procedures such as debridement, fasciotomy, or amputation.” They concluded that as this case suggests, infrared thermography can help inform clinicians in diagnosing and monitoring acute arterial ischemia.