Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 7  |  Issue : 3  |  Page : 260-264

Iatrogenic intra-arterial injection in the upper limb: A pragmatic guide for the on-call vascular surgeon


Department of Vascular Surgery, Doncaster Royal Infirmary, Doncaster, South Yorkshire, United Kingdom

Date of Submission22-Apr-2020
Date of Acceptance29-Apr-2020
Date of Web Publication12-Sep-2020

Correspondence Address:
Nandan Haldipur
Department of Vascular Surgery, Doncaster Royal Infirmary, Doncaster, South Yorkshire
United Kingdom
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijves.ijves_41_20

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  Abstract 


Background: Peripheral venous cannulation is one of the most commonly performed procedures to establish venous access in the hospital setting. Inadvertent arterial cannulation is a rare event but can have serious consequences including ischemia and limb loss, especially if medication is administered through the device. Vascular surgeons should have an understanding of the management of this potential complication Methods: We reviewed the risk factors, mechanism, pathophysiology, and management options for inadvertent upper limb arterial cannulation and injection. Results: Inadvertent arterial cannulation and administration of medication has a reported incidence of 1 in 3440 cases. Several risk factors were identified including difficult venous access, difficulty in communication, and aberrant vascular anatomy. Both arterial injury from the misplaced cannula and injection of medication can cause ischemic events through a number of mechanisms. We recommend that patients sustaining an inadvertent arterial injury should have an urgent clinical assessment and be managed according to the degree of upper limb ischemia as per the Rutherford classification. We provide a pragmatic management algorithm to aid the vascular surgeon when encountering such a situation. Conclusion: Iatrogenic arterial injury is a rare but potentially serious complication of peripheral venous cannulation. Prompt recognition and management of ischemic complications is essential for favorable outcomes. Our pragmatic management guide should aid the vascular surgeon in managing this situation.

Keywords: Cannulation, upper limb ischemia, vascular injury


How to cite this article:
Forsyth JM, Webster PJ, Haldipur N. Iatrogenic intra-arterial injection in the upper limb: A pragmatic guide for the on-call vascular surgeon. Indian J Vasc Endovasc Surg 2020;7:260-4

How to cite this URL:
Forsyth JM, Webster PJ, Haldipur N. Iatrogenic intra-arterial injection in the upper limb: A pragmatic guide for the on-call vascular surgeon. Indian J Vasc Endovasc Surg [serial online] 2020 [cited 2020 Sep 30];7:260-4. Available from: http://www.indjvascsurg.org/text.asp?2020/7/3/260/294906




  Introduction Top


Peripheral venous cannulation is the most commonly performed procedure to establish venous access in the hospital setting. Although thought of as routine in nature, complications are seen in up to 70% of patients including phlebitis, occlusion, dislodgment, and extravasation of infused medicines.[1] Inadvertent arterial cannulation and administration of medication is a rare event with a reported historical incidence between 1 in 3440 and 1 in 56,000 cases.[2],[3] Within the literature, there are numerous reports of severe ischemic injury following iatrogenic arterial cannulation,[4] however the true incidence of these serious complications is likely underreported due to medicolegal reasons. Given that 90% of patients attending the emergency department and 60% of all hospital inpatients will undergo peripheral venous cannulation,[1] it is likely that the modern-day vascular surgeon will encounter this complication several times during his/her career. This article aims to review the risk factors and pathophysiology of iatrogenic arterial injury as well as provide a pragmatic and evidence-based management algorithm for inadvertent intra-arterial injection.

Risk factors

The two sites in the upper limb that are particularly at risk of arterial puncture and potential vascular injury are the radial artery at the wrist and the brachial artery in the antecubital fossa. These sites lie in close proximity to the cephalic vein, which is the most frequently accessed vein for peripheral venous cannulation. Risk factors for intra-arterial injury include difficult venous access, morbid obesity, dark skin pigmentation, patients unable to communicate, thoracic outlet syndrome (vanishing radial pulse with abduction/internal rotation of the arm), and abnormal vascular anatomy.[5] With respect to the latter point, most injuries involve radial artery branches of the forearm and hand. The most commonly reported arterial anomaly of the upper limb is a high-rising radial artery that originates above the intercondylar line, resulting in a superficial branch.[6] This has a reported prevalence of 1%–14%.[7],[8] The radial artery terminates in a thin superficial palmar branch that stops in the thenar region or completes a scanty palmar arch with the ulnar artery. The palmar branch may also be inadvertently cannulated.

Another common anomaly is termed the “antebrachialis superficialis dorsalis artery,” which involves bifurcation of the radial artery in the forearm resulting in an anomalous superficial branch that terminates in an incomplete palmar arch. This superficial branch travels under a terminal branch of the cephalic vein just superficial to the radial styloid process, a common site of peripheral venous cannulation often termed the “houseman's vein.”

Pathophysiology of injury

Inadvertent cannulation of an artery itself can cause significant morbidity, including upper limb ischemia. Further complications can arise if the injury has not been identified and medication is delivered through the device. [Table 1] provides a list of commonly infused medications and their consequences if they are administered intra-arterially. Many processes are thought to be responsible for tissue ischemia occurring distal to the injection site. Some postulated mechanisms include inflammation of the endothelium, liberation of vasoactive amines, mechanical microcirculation occlusion, or a penetration of the plasma membrane of lipophilic substances with consequent lysis.[9] All concepts seem to agree on a final mechanism of peripheral underperfusion due to endarteritis, vasospasm, and thrombosis, leading to tissue necrosis.
Table 1: Commonly infused medications and their sequelae of intra-arterial administration[5],[12]

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Inadvertent injection of intra-arterial medication may manifest immediately, or several days following the event. At the time of infusion, patients may complain of discomfort at, or distal to, the site of injection. Patients who are unable to communicate, such as those intubated on intensive care, are therefore at particular risk of complications because they will not respond to the pain. Shortly after injection, patients may complain of altered sensation, motor deficits, and cutaneous manifestations such as flushing or mottling. In the worst-case scenario, patients may develop upper limb ischemia evidenced by pain, pallor, temperature changes, and loss of pulses.

Clinical assessment

A focused but thorough clinical assessment is the key to successfully managing these patients. The clinical history should ascertain when the cannula was inserted, what has been injected, when it was injected, and what the resultant effects are. There may be some investigative work required. For example, the cannula may have been inserted 2 days prior and different nurses may have injected different medications. By speaking to the nursing team and reviewing the medication chart, along with ascertaining when the symptoms started, it should be possible to identify the culprit medication. Sometimes, it may be very obvious, other times, it may not be. If it is a medication that is associated with severe ischemic damage [Table 1], the management approach should take this into account. To determine the severity of the ischemic symptoms, we recommend using Rutherford's classification of acute limb ischemia [Table 2]. If competent, we also recommend a point-of-care bedside arterial duplex assessment to ascertain the underlying vascular injury pattern.[10]
Table 2: Rutherford's classification of acute limb ischemia[16]

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Management of intra-arterial injection

Critical to patient outcome is the prompt recognition of upper limb ischemia. In the absence of any signs of ischemia, the cannula can be safely removed and the limb can be kept under close observation. On the contrary, if there is evidence of ischemia, the cannula should be left in situ as it can potentially be used for a diagnostic angiogram.

It is difficult to propose a specific management plan for such cases, as the nature of injury, pattern and degree of ischemia, and tissue damage will determine the exact management plan. However, if a case of limb ischemia requires intervention, then a suitable “workup” process will help prepare for all eventualities [Figure 1]. For any patient with Rutherford 2a or 2b ischemia prior to commencing treatment, we recommend the following approach, as per the European Society of Vascular Surgery (ESVS) guidelines on acute limb ischemia:[11]
Figure 1: Proposed algorithm for the management of iatrogenic intra-arterial injection

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  • Starve the patient
  • Oxygen therapy
  • Analgesia
  • Gain suitable venous access via the contralateral upper limb
  • Check relevant blood results (full blood count, renal function, clotting profile, and creatinine kinase levels)
  • Collect a group and sample (±crossmatch blood)
  • Intravenous fluids
  • Systemic intravenous heparin (as long as no bleeding concerns)
  • Perform ultrasound-guided mapping of a suitable lower limb great saphenous vein (GSV) as a potential bypass conduit (if no suitable GSV, then assess upper limb cephalic and basilic veins)
  • Upper limb arterial duplex or computed tomography angiogram upper limb.


For Rutherford 1 ischemia, the patient should be commenced on intravenous heparin for 24 h. Over this time, the limb should be closely observed for deterioration. For Rutherford 2a ischemia, again, the patient should be started on intravenous heparin, but the patient should also undergo a diagnostic angiogram. This, as mentioned before, should ideally be performed via the in-dwelling arterial cannula. Depending on the results of the angiogram, the patient should be considered for thrombolysis as a logical first step. However, there should be a low threshold for conversion to open surgery. For Rutherford 2b ischemia, patients should be commenced on intravenous heparin but taken to theatre for a definitive (and likely combined) procedure. Again, an on-table angiogram should be performed to “road-map” the vascular injury. At this point, on-table thrombolytic therapy may be considered. However, if the vascular injury is considerable and there are concerns regarding ischemic time, then deference to a quicker and invasive revascularization procedure should be considered. Direct exposure of the injured brachial/radial artery may be necessary, and an arterial repair at the site of cannulation may be necessary before potentially proceeding to embolectomy and/or bypass. In addition, a decompressive fasciotomy should be considered in cases of advanced ischemia, especially in those with delayed presentations.

For cases of Rutherford 3 ischemia, revascularization is not recommended. Such delayed cases should be referred to specialist plastic or orthopedic surgeons with an interest in upper limb pathology. The outcome for such patients is devastating and an upper limb amputation will likely be required.

The ESVS guidelines for acute limb ischemia[11] make it clear that most patients with upper limb ischemia are treated surgically by brachial embolectomy, and bypass surgery is rarely required acutely. The default should be surgery under local anesthesia, with an anesthetist present, with the option for intravenous sedation and resuscitation, if required. The ESVS guidelines also consider endovascular treatments such as percutaneous thrombectomy, aspiration thrombectomy, or catheter-directed thrombolysis (CDT) for acute upper limb ischemia. They emphasize that “only case reports exist to describe their benefits and complications.” However, the ESVS guidelines state that primary distal thrombosis of the hand may benefit from CDT.

Therapeutic considerations and controversies

There are other treatments that have been proposed to treat intra-arterial injection injuries. Lake and Beecroft[12] highlighted the following possible options: limb elevation (to improve venous and lymphatic drainage), local anesthetic injection (e.g. lidocaine) via the implicated cannula to prevent reflex vasospasm, and stellate ganglion blocks and lower-extremity sympathetic blocks to produce sustained arterial and venous vasodilatation. However, a pragmatic assessment of these approaches raises some concerns. Limb elevation can make ischemia worse, local anesthetic injections into arteries could trigger fatal cardiac arrhythmias, and nerve blocks can take a long time to organize and may not be successful.

Rai et al.[13] described the following management approaches: rest, analgesia, systemic heparinization, antiplatelet agents, and anti-sludging agents such as dextran. They also discussed intra-arterial injection of vasodilator agents and steroid therapy. However, in their case report of upper limb ischemia secondary to an ulnar artery injection injury, they saw no improvement with “conservative measures” which consisted of systemic heparin, dextran infusion, oral nifedipine 10 mg 8 hourly, and antiplatelet therapy. Indeed, they concluded that “such measures rarely suffice alone and aggressive therapy is mostly indicated.” In their case report, they encountered a dramatic improvement with thrombolytic therapy (urokinase at a dose of 50,000 units dissolved in 10 ml of normal saline injected via the brachial artery over 10 min followed by 200,000 units over the next 30 min)

Rautio and Keski-Nisula[14] reported a case series of seven patients who had injected oral formulations of drugs into an upper extremity artery. All patients underwent upper limb arteriography. Two patients were treated with local thrombolysis and two patients underwent fasciotomy. Combinations of clexane, aspirin, fragmin, and ilomedin were used for thrombosis prophylaxis (five patients). Good outcomes were found in only three of the seven patients. Two patients underwent amputation (antebrachium level and wrist level) and two patients required distal phalanx revision surgery. Delayed capillary refilling and/or impaired muscular strength was observed to predict severe vascular complications. All patients with angiographic findings of absent flow at the level of palmar arches or more proximally required amputations or revision surgery. Local thrombolysis did not improve outcomes. Although this patient group is slightly outside our proposed cohort, these findings highlight some important truths. Many of the “conservative” measures proposed in the management of these patients were not successful as many patients required surgery/amputations. Similarly, thrombolysis did not necessarily salvage the situation, and fasciotomy is not a “revascularization” procedure. Again, this does not mean thrombolysis and fasciotomy and conservative measures have no place. It does demonstrate that they are not foolproof techniques, and open surgery should not be avoided especially if the limb is imminently threatened.

Iblher et al.[9] reported the case of a 75-year-old woman who developed acute upper limb ischemia following an injection of diazepam into her left wrist for chronic pain. This was accidentally injected into the ulnar artery and caused ischemia of the 4th and 5th digits. The authors managed this with intravenous heparin and intra-arterial thrombolysis, which was followed by oral prostaglandin and aspirin therapy. She was a hospital inpatient for 10 days and saw only mild improvement. At 5-week outpatient follow-up, she had dry necrosis of her digits and required 4th digit amputation at the distal middle phalanx and the 5th digit was extra-articulated in the distal interphalangeal joint. In this case, the histology findings revealed small-vessel thrombosis. This case adds to the developing evidence base that conservative measures and thrombolysis serve as no guarantee of success.

In a final case report, Shon et al.[15] described a case of left thumb ischemia secondary to an iatrogenic injection of diclofenac into the radial artery. This was managed initially with oral beraprost 40 mg twice a day (prostaglandin therapy). Unfortunately, the patient's symptoms worsened, and ultimately required an amputation of the thumb tip. This highlights another unsuccessful example of conservative management.

The case reports discussed demonstrate that conservative measures can indeed fail and patients are at risk of requiring amputation if revascularization is not successful. Therefore, it would seem pragmatic and sensible to consider conservative measures and thrombolysis, but if they are not working effectively and/or time is limited, a more definitive and aggressive approach (ideally in a hybrid setting) should be adopted [Figure 1]. The evidence is generally lacking with regard to the management of acute upper limb ischemia, especially so in the context of upper limb arterial ischemia secondary to inadvertent intra-arterial injection. In agreement with the 2020 ESVS guidelines,[11] as thrombolysis has a limited evidence base for upper limb ischemia, we would veer more toward open surgical intervention for such patients. However, we recognize that thrombolysis does still have a place and should still be considered in the management approach.[16]


  Conclusion Top


Iatrogenic arterial injury is a rare complication of peripheral venous cannulation. Administration of medications in an inadvertently placed arterial cannula can have significant complications including upper limb ischemia with a risk of limb loss. Prompt recognition of ischemic complications is essential for favorable outcomes. Our pragmatic management guide should aid the vascular surgeon in managing this situation. A focused clinical assessment should ascertain the degree of ischemia according to the Rutherford classification and patients should be managed according to our proposed algorithm. We advise caution with regard to conservative measures and assert that it is better to treat these patients aggressively if there are any signs of limb threat.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Rodríguez-Calero MA, Blanco-Mavillard I, Morales-Asencio JM, Fernández-Fernández I, Castro-Sánchez E, de Pedro-Gómez JE. Defining risk factors associated with difficult peripheral venous Cannulation: A systematic review and meta-analysis. Heart Lung 2020. pii: S0147-9563 (20) 30009-1.  Back to cited text no. 1
    
2.
Cohen SM. Accidental intra-arterial injection of drugs. Lancet 1948;2:409-17.  Back to cited text no. 2
    
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Dundee JW. Thiopental and Other Barbiturates. Edinburgh: E.S Livingstone; 1956.  Back to cited text no. 3
    
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Lokoff A, Maynes JT. The incidence, significance, and management of accidental intra-arterial injection: A narrative review. Can J Anaesth 2019;66:576-92.  Back to cited text no. 4
    
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Sen S, Chini EN, Brown MJ. Complications after unintentional intra-arterial injection of drugs: Risks, outcomes, and management strategies. Mayo Clin Proc 2005;80:783-95.  Back to cited text no. 5
    
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Gonzalez-Compta X. Origin of the radial artery from the axillary artery and associated hand vascular anomalies. J Hand Surg Am 1991;16:293-6.  Back to cited text no. 6
    
7.
Mccormack LJ, Cauldwell EW, Anson BJ. Brachial and antebrachial arterial patterns; a study of 750 extremities. Surg Gynecol Obstet 1953;96:43-54.  Back to cited text no. 7
    
8.
Wood SJ, Abrahams PH, Sañudo JR, Ferreira BJ. Bilateral superficial radial artery at the wrist associated with a radial origin of a unilateral median artery. J Anat 1996;189(Pt 3):691-3.  Back to cited text no. 8
    
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Iblher N, Stark GB, Penna V. Necrosis of the 4th and 5th digits after intra-articular injection of diazepam into the wrist. Case Rep Surg 2011;2011:347523.  Back to cited text no. 9
    
10.
McCafferty J, Forsyth J. Point of Care Ultrasound Made Easy. 1st ed. Boca Raton, FL: CRC Press; 2020.  Back to cited text no. 10
    
11.
Björck M, Earnshaw JJ, Acosta S, Bastos Gonçalves F, Cochennec F, Debus ES, et al. Editor's Choice – European Society for Vascular Surgery (ESVS) 2020 clinical practice guidelines on the management of acute limb ischaemia. Eur J Vasc Endovasc Surg 2020;59:173-218.  Back to cited text no. 11
    
12.
Lake C, Beecroft C. Extravasation injuries and accidental intra-arterial injection. Continuing Education in Anaesthesia. Crit Care Pain 2010;10:109-13.  Back to cited text no. 12
    
13.
Rai KM, Rao KS, Maudar KK. Accidental intra-arterial drug injection: A case report. Med J Armed Forces India 1997;53:137-9.  Back to cited text no. 13
    
14.
Rautio R, Keski-Nisula L. Inadvertent intra-arterial drug injections: The role of angiographic and clinical findings. Acta Radiol 2006;47:554-8.  Back to cited text no. 14
    
15.
Shon HC, Park JK, Kang SW, Yang JY. Necrosis of the thumb after inadvertent injection of diclofenac in the radial artery: A case report. J Pain Res 2017;10:2803-6.  Back to cited text no. 15
    
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Sidawy A, Perler B. Rutherford's Vascular Surgery and Endovascular Therapy. 9th ed. Philadelphia: Elsevier; 2019.  Back to cited text no. 16
    


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