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The incidence, significance, and management of accidental intra-arterial injection: a narrative review

  • Andrew LokoffEmail author
  • Jason T. Maynes
Review Article/Brief Review
  • 29 Downloads

Abstract

This narrative review discusses the incidence, risk factors, mechanisms of injury, complications, and treatment regimens for accidental intra-arterial injection of medications. Despite awareness of the issue and the establishment of safety recommendations by national agencies, accidental iatrogenic intra-arterial injection of medications continues to occur. Most of these injuries are caused by accidental injection into an established arterial cannula or the inadvertent and unrecognized cannulation of an artery instead of a vein. Although many medications have been injected into arteries without significant consequence, a number of drugs are consistently associated with severe morbidity, including the need for amputation, making early incident recognition and treatment vital. Accidental intra-arterial injection of medications has also been increasingly reported in those who use illicit drugs, as these intravenous injection attempts can be misdirected into an artery. These reports have improved understanding of these injuries and possible treatment modalities. While the characteristics of injuries from illicit injections are diverse and the optimal treatment modalities are still uncertain, a regimen that includes anticoagulation and intra-arterial injection of thrombolytics and prostaglandins may improve outcomes. Steroids, vasodilators, and sympathetic blocks do not appear to influence amputation rates. Owing to the small and sporadic number of cases, no definitive clinical trial evidence exists, but the treatment modalities found to be useful in the illicit intra-arterial injection group may benefit treatment of similar iatrogenic injuries.

Incidence, importance et prise en charge des injections intra-artérielles accidentelles: un compte rendu narratif

Résumé

Ce compte rendu narratif traite de l’incidence, des facteurs de risque, des mécanismes de lésion, des complications et des régimes thérapeutiques lors de l’injection intra-artérielle accidentelle de médicaments. Malgré la reconnaissance de ce problème et la mise en place de recommandations de sécurité par les organismes nationaux, les injections intra-artérielles iatrogéniques accidentelles de médicaments surviennent encore. La plupart de ces lésions sont provoquées par l’injection accidentelle dans une canule artérielle déjà en place ou la canulation par inadvertance et non reconnue d’une artère au lieu d’une veine. Bien que de nombreux médicaments aient été injectés dans des artères sans conséquence importante, plusieurs médicaments sont régulièrement associés à une morbidité grave, notamment au recours à l’amputation, ce qui rend essentiels tant l’identification que le traitement rapides de l’incident. L’injection intra-artérielle accidentelle de médicaments est également rapportée de manière plus fréquente chez les personnes utilisant des drogues illicites, étant donné que ces tentatives d’injection intraveineuse peuvent accidentellement se retrouver en intra-artériel. Ces comptes rendus ont amélioré la compréhension de ces lésions et les modalités de traitement possibles. Alors que les caractéristiques des lésions provoquées par des injections illicites varient beaucoup et que les modalités optimales de traitement demeurent incertaines, un régime thérapeutique incluant une anticoagulation et l’injection intra-artérielle d’agents thrombolytiques et de prostaglandines pourrait améliorer les pronostics. Les stéroïdes, les vasodilatateurs et les blocs sympathiques ne semblent pas avoir d’impact sur les taux d’amputation. En raison du petit nombre de cas et de leur aspect sporadique, aucune donnée probante définitive tirée d’une étude clinique n’existe, mais les modalités de traitement qui se sont avérées utiles dans le groupe d’injection intra-artérielle illicite pourraient également être bénéfiques pour traiter des lésions iatrogéniques semblables.

Notes

Acknowledgement

Jason T. Maynes would like to thank the Wasser Family and SickKids Foundation as the holder of the Wasser Chair in Anesthesia and Pain Medicine.

Conflicts of interest

None declared.

Editorial responsibility

This submission was handled by Dr. Hilary P. Grocott, Editor-in-Chief, Canadian Journal of Anesthesia.

Author contributions

Andrew Lokoff researched and wrote the manuscript. Jason T. Maynes edited and adjudicated the paper.

Funding

None.

References

  1. 1.
    Fell JN. Intra-arterial injection of tubocurarine and thiopentone. Br Med J 1953; 1: 95-6.CrossRefPubMedCentralGoogle Scholar
  2. 2.
    Treiman GS, Yellin AE, Weaver FA, Barlow WE, Treiman RL, Gaspar MR. An effective treatment protocol for intraarterial injection. J Vasc Surg 1990; 12: 456-65.CrossRefPubMedGoogle Scholar
  3. 3.
    Ipaktchi K, Ipaktchi R, Niederbichler AD, Vogt PM, Knobloch K. Unrecognized hand ischemia after intraarterial drug injection: successful management of a “near miss” event. Patient Saf Surg 2008; 2: 32.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Righini M, Angellillo-Scherer A, Gueddi S, Le Gal G, Bounameaux H. Management of severe ischemia of the hand following intra-arterial injection. Thromb Haemost 2005; 94: 219-21.CrossRefPubMedGoogle Scholar
  5. 5.
    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.CrossRefPubMedGoogle Scholar
  6. 6.
    Mariyaselvam M, Hutton A, Young P. Accidental intra-arterial injection: an under-reported never event. Crit Care 2015; 19(Suppl 1): 166.CrossRefGoogle Scholar
  7. 7.
    Beattie WS, Culwick MD, Grocott HP. Canadian Anesthesia Incident Reporting System (CAIRS): The Canadian Anesthesiologists’ Society’s National Patient Safety Initiative. Can J Anesth 2018; 65: 749-56.CrossRefGoogle Scholar
  8. 8.
    Mazumder JK, Metcalf IR, Holland AJ. Inadvertent intra-arterial injection of thiopentone. Can Anaesth Soc J 1980; 24: 395-8.CrossRefGoogle Scholar
  9. 9.
    Rees M, Dormandy J. Accidental intra-arterial injection of diazepam. Br Med J 1980; 26: 289-90.CrossRefGoogle Scholar
  10. 10.
    Chong M, Davis PT. Accidental intra-arterial injection of propofol. Anaesthesia 1987; 42: 781.CrossRefPubMedGoogle Scholar
  11. 11.
    Marsch SC, Schafer HG. An accidental intra-arterial injection of midazolam through a 3-way stop cock in an arterial flushing system (German). Anaesthesist 1990; 39: 337-8.PubMedGoogle Scholar
  12. 12.
    Holley H, Cuthrell L. Intraarterial injection of propofol. Anesthesiology 1990; 73: 183-4.CrossRefPubMedGoogle Scholar
  13. 13.
    Andreev A, Kavrakov T, Petkov D, Penkov P. Severe acute hand ischemia following accidental intraarterial drug injection, successfully treated with thrombolysis and intraarterial iloprost infusion. Angiology 1995; 46: 963-7.CrossRefPubMedGoogle Scholar
  14. 14.
    Jones NC. Inadvertent intra-arterial injection of drugs. Why does it still occur? Br J Intensive Care 1995; 5: 166-8.Google Scholar
  15. 15.
    Ozel A, Yavuz H, Erkul I. Gangrene after penicillin injection (a case report). Turk J Pediatr 1995; 37: 67-71.PubMedGoogle Scholar
  16. 16.
    Kessell G, Barker I. Leg ischaemia in an infant following accidental intra-arterial administration of atracurium treated with caudal anaesthesia. Anaesthesia 1996; 51: 1154-6.CrossRefPubMedGoogle Scholar
  17. 17.
    Joist A, Tibesku CO, Neube M, Frerichmann U, Joosten U. Gangrene of the fingers caused by accidental intra-arterial injection of diazepam (German). Dtsch Med Wochenschr 1999; 124: 755-8.CrossRefPubMedGoogle Scholar
  18. 18.
    Ohana E, Sheiner E, Gurman GM. Accidental intra-arterial injection of propofol. Eur J Anaesthesiol 1999; 16: 569-70.CrossRefPubMedGoogle Scholar
  19. 19.
    Duggan M, Braude BM. Accidental intra-arterial injection through and ‘intravenous’ cannula on the dorsum of the hand. Paediatr Anaesth 2004; 14: 611-2.CrossRefPubMedGoogle Scholar
  20. 20.
    Saad S, Horn J. Accidental intra-arterial injection of midazolam and pethidine during endoscopy: a reminder that a routine procedure can result in disaster. Endoscopy 2007; 39(Suppl 1): E198-9.CrossRefPubMedGoogle Scholar
  21. 21.
    Mirzatolooei F, Afshar A. Intravenous injection of Diazepam to cubital vein can be complicated by accidental intra-arterial penetration and gangrene. Arch Iranian Med 2008; 11: 469-71.Google Scholar
  22. 22.
    Mitani S, Ishiyama T, Matsukawa T. Inadvertent intraarterial injection of propofol in a patient under general anesthesia. J Anesth 2009; 23: 307.CrossRefPubMedGoogle Scholar
  23. 23.
    Kjaergaard M, Rovsing ML. Accidental intra-arterial propofol injection (Danish). Ugeskr Laeger 2010; 172: 1383-4.PubMedGoogle Scholar
  24. 24.
    Aghoutane EM, Fezzazi R, Elhaouati R, Boumzebra D. Fingers necrosis after an accidental intra-arterial injection o fluvloxacilline: case report (French). Chir Main 2011; 30: 120-2.CrossRefPubMedGoogle Scholar
  25. 25.
    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; DOI:  https://doi.org/10.1155/2011/347523.
  26. 26.
    Lehavi A, Sandler A, Netzer A, Katz YS. Vascular injury following accidental intra-arterial injection of clindamycin: adverse drug reaction report. Minerva Anestesiol 2011; 77: 468-9.PubMedGoogle Scholar
  27. 27.
    Jain A, Sahni N, Banik S, Solanki SL. Accidental intra-arterial injection of neostigmine with glycopyrrolate or atropine for reversal of residual neuromuscular block: a report of two cases. Anesth Analg 2012; 115: 210-1.CrossRefPubMedGoogle Scholar
  28. 28.
    Dutton RP. A case report from the anesthesia incident reporting system. Anesthesiology 2011; 75: 31-2.Google Scholar
  29. 29.
    Prabhu R, Shenoy R, Thinda N, Patel A, Sadhu S. Be careful with an iv line. J Clin Diagn Res 2014; 8: 166-7.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Shenoi AN, Fortenberry JD, Kamat P. Accidental intra-arterial injection of propofol. Pediatr Emerg Care 2014; 30: 136.CrossRefPubMedGoogle Scholar
  31. 31.
    Shukla A, Ghaffar ZBA, Joshi S. Inadvertent intra arterial injection of rocuronium: a case report. The Internet Journal of Anesthesiology 2008; 19.Google Scholar
  32. 32.
    Samanta S, Chakraborty N, Samanta S. Accidental intra-arterial injection of paracetamol: different preparations, different results. Eur J Anaesthesiol 2014; 31: 236-7.CrossRefPubMedGoogle Scholar
  33. 33.
    Kozar S, Kurnik G. Accidental intra arterial injection of ephedrine: what about treatment with nitroglycerine. J Anesth Clin Res 2015; DOI:  https://doi.org/10.4172/2015-6148.1000510.
  34. 34.
    Singh A, Sidhu KS, Rai S. Accidental intra-arterial injection during test dose of injection of benzyl penicillin: complications and management - a case report. Case Rep Clin Med 2015; 4: 222-6.CrossRefGoogle Scholar
  35. 35.
    Witkowski M, Mochmann HC, Rauch U, Knie W, Landmesser U, Skurk C. Acute thrombotic occlusion of the left brachial artery after intra-arterial administration of amiodarone. Crit Care Med 2016; 44: e227-30.CrossRefPubMedGoogle Scholar
  36. 36.
    Ghatak T, Samanta S. Accidental intra-arterial dexmedetomidine injection in postoperative ward. Anaesth Intensive Care 2013; 41: 431.PubMedGoogle Scholar
  37. 37.
    Hanci V, Ozbilgin S, Ozbal S, et al. Evaluation of the effects of intra-arterial sugammadex and dexmedetomidine: and experimental study. Braz J Anesthesiol 2016; 66: 456-64.CrossRefPubMedGoogle Scholar
  38. 38.
    Lokoff A, Lokoff P. Unrecognized arterial cannulation due to the backflow feature of the BD Insyte™ Autoguard™ BC Cannula. Can J Anesth 2015; 62: 542-3.CrossRefPubMedGoogle Scholar
  39. 39.
    Kapoor I, Mahajan C, Prabhakar H. An unintended cannulation of aberrant radial artery! Karnataka Anaesth J 2015; 1: 220-1.CrossRefGoogle Scholar
  40. 40.
    Shivappagoudar VM, George B. Unintentional arterial cannulation during cephalic vein cannulation. Indian J Anaesth 2013; 57: 320-2.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Beale EW, Behnam A. Injection injury of and aberrant superficial radial artery requiring surgical intervention. J Hand Microsurg 2012; 4: 39-42.CrossRefPubMedGoogle Scholar
  42. 42.
    Leslie RA, Gouldson S, Harris N, et al. Management of arterial lines and blood sampling in intensive care: a threat to patient safety. Anaesthesia 2013; 68: 1114-9.CrossRefPubMedGoogle Scholar
  43. 43.
    Fikkers BG, Wuis EW, Wijnen MH, Scheffer GJ. Intraarterial injection of anesthetic drugs. Anesth Analg 2006; 103: 792-4.CrossRefPubMedGoogle Scholar
  44. 44.
    Knill RL, Evans D. Pathogenesis of gangrene following intra-arterial injection of drugs: a new hypothesis. Can Anaesth Soc J 1975; 22: 637-46.CrossRefPubMedGoogle Scholar
  45. 45.
    Samanta S, Samanta S. Accidental intra arterial injection of diclofenac sodium and their consequences: report of two cases. Anaesth Pain Intensive Care 2013; 17: 101-2.Google Scholar
  46. 46.
    Chang YS, Lin CF, Wu CL, et al. Mechanism underlying benzyl alcohol cytotoxicity (triamcinolone acetonide preservative) in human epithelial cells. Investigative Ophthalmol Visual Sci 2011; 52: 4214-22.CrossRefGoogle Scholar
  47. 47.
    Chang YS, Tseng SY, Tseng SH, Wu CL, Chen MF. Traimcinolone acetonide suspension toxicity to corneal endothelial cells. J Cataract Refract Surg 2006; 32: 1549-55.CrossRefPubMedGoogle Scholar
  48. 48.
    Chang YS, Wu CL, Tseng SH, Kuo PY, Tseng SYl. In vitro benzyl alcohol cytotoxicity: implications for intravitreal use of triamcinolone acetonide. Exp Eye Res 2008; 86: 942-50.Google Scholar
  49. 49.
    MacPherson RD, McLeod LJ, Grove AJ. Intra-arterial thiopentone is directly toxic to vascular endothelium. Br J Anaesth 1991; 67: 546-52.CrossRefPubMedGoogle Scholar
  50. 50.
    MacPherson RD, Rasiah RL, McLeod LJ. Intraarterial propofol is not directly toxic to vascular endothelium. Anesthesiology 1992; 76: 967-71.CrossRefPubMedGoogle Scholar
  51. 51.
    Petros AJ, Bogle RG, Pearson JD. Propofol stimulates nitric oxide release from cultured porcine aortic endothelial cells. Br J Pharmacol 1993; 109: 6-7.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Wang B, Luo T, Chen D, Ansley DM. Propofol reduces apoptosis and up-regulates endothelial nitric oxide synthase protein expression in hydrogen peroxide-stimulated human umbilical vein endothelial cells. Anesth Analg 2007; 4: 1027-33.CrossRefGoogle Scholar
  53. 53.
    Hofbauer R, Frass M, Salfinger H, et al. Propofol reduces the migration of human leukocytes through endothelial cell monolayers. Crit Care Med 1999; 27: 1843-7.CrossRefPubMedGoogle Scholar
  54. 54.
    Sandoo A, van Zanten JJ, Metsios GS, Carroll C, Kitas GD. The endothelium and its role in regulating vascular tone. Open Cardiovasc Med J 2010; 4: 302-12.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Yau J, Teoh H, Verma S. Endothelial cell control of thrombosis. BMC Cardiovasc Disord 2015; 15: 130.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Kinmonth JB, Shepherd RC. Accidental injection of thiopentone into arteries: studies of pathology and treatment. BMJ 1959; 2: 914-8.CrossRefPubMedGoogle Scholar
  57. 57.
    Crawford CR, Terranova WA. The role of intraarterial vasodilators in the treatment of inadvertent intraarterial injection injuries. Ann Plast Surg 1990; 25: 279-82.CrossRefPubMedGoogle Scholar
  58. 58.
    Roberts JR, Krisanda TJ. Accidental intra-arterial injection of epinephrine treated with phentolamine. Ann Emerg Med 1989; 18: 424-5.CrossRefPubMedGoogle Scholar
  59. 59.
    Simon RW, Pfammatter T, Amann-Vesti BR. Accidental intraarterial cocaine injection. J Vasc Interv Radiol 2008; 19: 1124-5.CrossRefPubMedGoogle Scholar
  60. 60.
    Waters DJ. Intra-arterial thiopentone. A physico-chemical phenomenon. Anaesthesia 1966; 21: 346-56.CrossRefPubMedGoogle Scholar
  61. 61.
    Goldberg I, Bahar A, Yosipovich Z. Gangrene of the upper extremity following intra-arterial injection of drugs. A case report and review of the literature. Clin Orthop Relat Res 1984; 188: 223-9.Google Scholar
  62. 62.
    Rohm S, Staab H, Schulz H, Richtr O, Aust G. Good clinical outcome after accidental intra-arterial injection of Flunitrazepam tablets in 16 drug abusers with critical limb ischemia. Eur J Vasc Endovasc Surg 2014; 47: 61-7.CrossRefPubMedGoogle Scholar
  63. 63.
    Chang MY, Lin JL. Irreversible ischemic hand following intraarterial injection of zolpidem powder. J Toxicol Clin Toxicol 2003; 417: 1025-8.CrossRefGoogle Scholar
  64. 64.
    Khan S, Stannard N, Greijn J. Precipitation of thiopental with muscle relaxants: a potential hazard. JRSM Short Rep 2011; 2: 58.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Breguet R, Terraz S, Righini M, Didier D. Acute hand ischemia after unintentional intraarterial injection of drugs; is catheter-directed thrombosis useful? J Vasc Interv Radiol 2014; 25: 963-8.CrossRefPubMedGoogle Scholar
  66. 66.
    Hering J, Angelkort B. Acute ischemia of the hand after intra-arterial injection of flunitrazepam. Local combined fibrinolysis therapy in three cases (German) Dtsch Med Wochenschr 2006; 131: 1377-80.Google Scholar
  67. 67.
    Silverman SH, Turner WW Jr. Intraarterial drug abuse: new treatment options. J Vasc Surg 1991; 14: 111-6.CrossRefPubMedGoogle Scholar
  68. 68.
    Rautio R, Keski-Nisula L. Inadvertent intra-arterial drug injections: the role of angiographic and clinical findings. Acta Radiol 2006; 6: 554-8.CrossRefGoogle Scholar
  69. 69.
    Bittner CH, Zuber M, Eisner L. Acute ischemia of the hand in a drug addict after accidental intra-arterial injection (German). Swiss Surg 2002; 8: 281-4.CrossRefPubMedGoogle Scholar
  70. 70.
    Leifert JA, Bossaller L, Uhl M. Acute ischaemia of the leg following accidental intra-arterial injection of dissolved flunitrazepam tablets. Vasa 2008; 37: 374-8.CrossRefPubMedGoogle Scholar
  71. 71.
    Radeleff B, Stampfl U, Sommer CM, et al. Successful thrombolysis and spasmolysis of acute leg ischemia after accidental intra-arterial injection of dissolved flunitrazepam tablets. Cardiovasc Intervent Radiol 2011; 34: 1085-9.CrossRefPubMedGoogle Scholar
  72. 72.
    Hohenstien C, Herdtle S, Hoyme M, Lauten A, Chaudhary T. Rescue of the limb after accidental injection of diazepam into femoral artery. Am J Emerg Med 2014; 32(1149): e5-6.Google Scholar
  73. 73.
    Gouny P, Gaitz JP, Vayssairat M. Acute hand ischemia secondary to intraarterial buprenorphine injection: treatment with iloprost and dextran-40—a case report. Angiology 1999; 50: 605-6.CrossRefPubMedGoogle Scholar
  74. 74.
    Samuel I, Bishop CC, Jamieson CW. Accidental intra-arterial drug injection successfully treated with iloprost. Eur J Vasc Surg 1993; 7: 93-4.CrossRefPubMedGoogle Scholar
  75. 75.
    Seak C, Kooi XJ, Seak CJ. Acute hand ischemia after intra-arterial injection of meprobamate powder. J Emerg Med 2012; 43: 468-71.CrossRefPubMedGoogle Scholar
  76. 76.
    Devulappalli C, Han KD, Bello RJ, LaPorte DM, Hepper CT, Katz RD. Inadvertent intra-arterial drug injections in the upper extremity: systematic review. J Hand Surg Am 2015; 40: 2262-8.CrossRefGoogle Scholar
  77. 77.
    Razavi MK, Lee DS, Hofmann LV. Catheter-directed thrombolytic therapy for limb ischemia: current status and controversies. J Vasc Interv Radiol 2004; 15: 13-23.CrossRefPubMedGoogle Scholar
  78. 78.
    Rai KM, Rao KS, Maudar KK. Accidental intra-arterial drug injection: a case report. Med J Armed Forces India 1997; 53: 137-9.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Canadian Anesthesiologists' Society 2019

Authors and Affiliations

  1. 1.Department of Anesthesia and Pain MedicineHospital for Sick ChildrenTorontoCanada
  2. 2.Department of AnesthesiaUniversity of TorontoTorontoCanada

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