Eur J Vasc Surg 6, 430-433 (1992)
CASE REPORT Accidental Intra-arterial Injection in Drug Addicts J. C. Cooper 1, A. B. Griffiths 2, R. B. Jones 2 and A. T. Raftery I
1Department of Surgery, The Royal Hallamshire Hospital, Sheffield, U.K. and 2Department of Surgery, Rotherham District General Hospital, Rotherham, U.K. This paper reports on our experience of vascular insufficiencyfollowing accidental intra-arterial injection in drug addicts and discusses possible treatment options and pathophysiology. Key Words: Drug abuse; Drug addiction; Injection intra-arterial).
Introduction Inadvertent intra-arterial injection of drugs is a rare but well-recognised complication of anaesthetic practice. 1-3 Such an event can cause severe tissue necrosis and gangrene, although the exact mechanism by which this produces such a dramatic effect is obscure. 4 With the increasing prevalence of drug addiction, accidental intra-arterial injection is being seen in this group of patients. A variety of substances may be injected, and complications arising from this can be difficult to treat. We report our experience of five instances of inadvertent intra-arterial injection in drug addicts, and_ discuss the treatment options and pathophysiology.
Case Reports
Case 1 In December 1987 a 26-year-old male drug addict presented as an emergency, l h following accidental injection of his left radial artery at the wrist with a suspension of crushed temazepam, codeine phosphate and diazepam tablets, which had been dissolved in tap water. He complained of immediate severe pain in the hand which on admission was ischaemic, with cyanosis and anaesthesia of all Please address all correspondence to: J. C. Cooper, RoyalHallamshire Hospital, Glossup Road, Sheffield,U.K. 0950-821X/92/040430+04 $03.00/0© 1992Grune & StrattonLtd.
fingers. He had normal brachial and ulnar pulses, and a weak radial pulse which became impalpable shortly after admission. An intravenous (i.v.) infusion of prostacyclin was commenced in combination with a stellate ganglion block, but the hand remained ischaemic. An arteriogram revealed an occluded radial artery from its origin, patent ulnar and interosseous arteries to the wrist and absent digital arteries with sluggish flow in the palm. An intraarterial infusion of streptokinase was commenced and given for 24h without improvement. Seventytwo hours following injection the patient became toxic, and the hand and forearm remained ischaemic and became oedematous. An X-ray of the forearm revealed gas in the subcutaneous tissues and an above-elbow amputation was carried out following which the patient made a good recovery. Bacteriology of the muscle taken from the hand and forearm revealed Clostridium perfringens. Histologically the radial and digital arteries were found to be thrombosed and to contain particulate foreign body material. In addition there was widespread tissue necrosis with Gram-positive cocci in the tissues. In September 1989 the same patient re-presented I h after accidental injection of his right femoral artery at the groin with a suspension of crushed triazolam tablets dissolved in tap water. He complained of severe pain in his thigh and leg which was cold and mottled. All peripheral pulses were initially palpable. He was commenced on i.v. heparin and subsequently prostacyclin, but within 12 h the leg had become very tense and swollen, and remained cyanosed. He
Accidental Intra-arterial Injection
underwent thigh and leg fasciotomies but this failed to improve the situation. His general condition deteriorated and he became very toxic and developed acute renal failure requiring haemodialysis. Thirty-six hours following admission he underwent emergency disarticulation of the left leg through the hip, from which he recovered slowly. Histology revealed extensive vascular thrombosis secondary to occlusion of the small arteries with refractive foreign material and patchy myonecrosis.
Case 2
In May 1988 a 34-year-old male drug addict presented 3 h following inadvertent injection of his right radical artery at the wrist with a solution of 150 mg of cyclizine. He had developed severe pain in his hand and fingers, and on admission the radial three digits were very painful, pale and cool with reduced sensation. His radial and ulnar pulses were both palpable. He was treated with i.v. heparin, analgesia and antibiotics. The radial three fingers remained acutely painful and swollen for several days, but this subsequently settled and the circulation improved. The tips of the thumb and index finger remained tender for several weeks but amputation was avoided.
Case 3
In October 1989 a 31-year-old female drug addict presented l h after accidental injection of her left radial artery in the anatomical snuff box with a suspension of five crushed DF118 tablets dissolved in 5ml of boiled tap water. She complained of immediate severe burning pain in the left hand and forearm which was ischaemic with cyanotic mottling to just proximal to the elbow. All major pulses were palpable. An urgent arteriogram revealed patent brachial, ulnar and radial arteries, but occlusion of the superficial and deep palmar arch arteries and no filling of the digital arteries. She was commenced on intra-arterial praxilene for 24 h and i.v. heparin, with some improvement of the circulation to her forearm, but the hand and in particular the fingers remained very ischaemic. The following day a left cervical sympathectomy was performed with some relief of the pain and improvement in the circulation of the hand. Intravenous heparin and praxilene were continued, and over the next few days she developed dry gangrene of the finger tips and subsequently, ampu-
431
tation through the proximal phalanges of all digits was performed.
Case 4
In January 1989 a 24-year-old male drug addict presented 36 h following accidental injection of his right femoral artery at the groin with a solution of methadone. On admission his foot was cold, cyanosed, painful and numb, and the calf was very swollen and tense. There were no palpable pulse below the femoral artery. An arteriogram revealed normal femoral and popliteal arteries, but poor flow in the tibial vessels. Open fasciotomies of the leg were performed, and the following day the foot became warm and pink with palpable pulses. Apart from a transient period of acute renal failure and myoglobinuria, the patient made a full recovery.
Discussion
The true incidence of accidental intra-arterial injection in drug addicts in the U.K. is unknown, but with the prevalence of drug addiction in recent years it would seem likely that it is on the increase. Certainly evidence from North America suggests the problem is becoming more common, s The covert nature of illicit drug administration means, of course, that only those addicts who develop the most severe complications are likely to seek medical help; we believe, however, that because they often use impure substances, 6 ischaemic complications are likely to occur and bring the patients promptly to the physician. In anaesthetic practice the incidence of intra-arterial injection has been variously estimated from i in 8000 to I in 55 000. 7 The most common agent reported in this situation is thiopentone, 2"3"7'8 although other drugs have been shown to produce ischaemic complications.9' 10 Exactly w h y medications which can be given safely i.v. produce catastrophic results when injected intra-arterially is not entirely clear, but several theories have been suggested based on clinical and experimental data. Burn 2"11 proposed that vasoconstriction due to the release of noradrenalin from the arterial wall was the main factor. It has been shown, however, by Kinmouth and Shepherd 12 that although thiopentone can produce experimental vasoconstriction its effect is short lived, and thereafter there is a rapid return to normal or even vasodiEur J VascSurg Vol 6, July1992
432
J.C. Cooper et al.
latation. These workers, supported by others, 4"13 attributed more significance to primary endothelial arteriolar damage distal to the site of injection, leading to necrosis of the arteriolar wall and then thrombosis. A criticism of this theory, however, is that thrombosis is probably too slow a process to account for the suddenness of the onset of symptoms, and Waters 3 proposed the formation of insoluble drug crystals. He showed experimentally that when a solution of sodium thiopentone was mixed with arterial blood it formed a precipitate of insoluble crystals, which in part was due to rapid pH changes and the formation of acid thiopentone. On the basis of this evidence, he suggested that the crystals caused an immediate mechanical arteriolar blockage which accounted for the rapid onset of symptoms. In addition the crystals provoked a release of noradrenalin from the arteriolar wall. When both the mechanical and humoral factors operated for long enough, stagnation of blood occurred leading to arteriolar thrombosis which then spread in a retrograde fashion to the main arteries. This theory is supported by our own experience of intra-arterial injection, not of crystals but of a particulate suspension, which may have similar effects on the arterioles. Immediate ischaemia followed by gangrene was a universal complication when a suspension was injected, due to particulate micro-emboli lodging in the arterioles. Interestingly, although the cases showed signs of ischaemia, all had palpable major pulses at the time of presentation, presumably because retrograde thrombosis had not yet occurred. Further proof that particulate matter was injected came from the histology from case 1, where birefringent particles were seen in the digital arteries. By contrast, when pure solutions of cyclizine and methadone were used in cases 2 and 4, symptoms developed rather more gradually and a relatively favourable outcome was achieved without amputation. We must assume in both these cases that cyclizine and methadone do not precipitate out in the arterial blood, and hence symptoms were mainly due to spasm and oedema which was relatively short lived. It may be inferred that the commonly injected substances (e.g. morphine) do not precipitate either, as few cases of serious complications following their administration have been encountered. If this mechanism is indeed true, it would explain the difficulties encountered by ourselves and others in the treatment of this condition when a suspension is injected. Various treatments have previously been recommended. These include vasodilators in combination with antibiotics, although Eur J Vasc Surg Vol 6, July 1992
whether this avoids amputation is doubtful. Kinmouth and Shepherd 12 showed experimentally that the incidence of gangrene in rabbits' ears following injection of thiopentone could be reduced by sympathectomy and heparinisation. Fasciotomy has been recommended when swelling and spasm is present, s This proved useful in case 4 when a solution was injected, and we would advocate its use in this situation. Intermittent positive pressure is claimed by other workers 14 to reduce the need for fasciotomy and promote the return of circulation. From our limited experience and that of others including a study from North America s it would seem that no single treatment is of particular value when a suspension has been injected. This is perhaps not surprising as none of the measures attack the root of the problem, i.e. dislodgement of micro-emboli from the small vessels. What is needed is a means of mechanically dislodging the emboli or dissolving them, and at present no such treatment is available. We would, however, recommend the following measures in such cases presenting with ischaemia following intra-arterial injection of a suspension of particulate matter. Antibiotics should be commenced immediately to reduce the risk of gas gangrene, and sympathectomy, either chemical or operative, may dilate up the arteriolar bed, theoretically allowing the precipitate to lodge more distally. (As an alternative systemic vasodilator therapy could be used). In addition, we would recommend i.v. anti-coagulation in an attempt to reduce retrograde thrombosis, and fasciotomy should certainly be considered if considerable swelling is present. We believe, nevertheless, that if a suspension, or a solution producing micro-emboli has been injected, distal gangrene may unavoidably develop whatever treatment is given and amputation sadly become necessary.
Acknowledgement We wish to thank Mrs C. Bagshaw for typing the manuscript.
References 1 BRowN SS, MORRELLL, DUNDEEJW. Intra-arterial barbiturates. Br ] Anaesth 1968; 40: 13-19. 2 BURN JH. Why thiopentone injected into an artery may cause gangrene. Br Med ] 1960; 2: 414-416. 3 WATERSDJ. Intra-arterial thiopentone. Anaesthesia 1966; 2: 346356.
Accidental Intra-arterial Injection
4 ENGLERHS, FREEMAN RA, KANAVAGECCB, OGDEN LL, MORETZ WH. Production of gangrene extravasaties by intra-arterial injections. Am Surg 1964; 30: 602-607. 5 BERGNERR, BENITEZ P. Surgical emergencies from intravascular injection of drugs. In: BERGANJJ, YAO JST, eds. Vascular Surgical Emergencies. London: Grune & Stratton, 1987; 309-325. 6 HAWKINSLG, LlSCHER CG, SWEENEYM. The main line accidental intra-arterial drug injection. Clin Orthop 1973; 94: 268-274. 7 COHEN SM. Accidental intra-arterial injection of drugs. Lancet 1948; 2: 361-371. 8 STONE HH, DONNELLYCC. The accidental intra-arterial injection of thiopentone. Anaesthesia 1961; 22: 995-1006. 9 KING Iq, HAWTOFDB. Accidental intra-arterial injection of ether. JAMA 1963; 184: 241-242.
433
10 BATIST G. Gangrene of the arm after intravenous injection of 'chlorpromazine. Rass Cliniosci 1960; 36: 113-114. 11 BURN JH, HOBBS R. Lancet 1959; 1: 1112-1114. 12 KINMOUTH BJ, SHEPHERD RC. Accidental injection of thiopentone into arteries. Br Med J 1959; 2: 914-916. 13 HAGER DL, WILSON JN. Gangrene of the hand following intraarterial injection. Arch Surg 1967; 94: 86-89. 14 ENGLERHS, PURVISJG, KANAVAGECCB, OGDENLL, FREEMANBS, MORITZ WH. Gangrene extremities resulting from intra-arterial injections. Arch Surg 1967; 94: 644-651.
Accepted 7 November 1990
Eur J Vasc Surg Vol 6, July 1992
CASE REPORT Accidental Intra-arterial Injection in Drug Addicts J. C. Cooper 1, A. B. Griffiths 2, R. B. Jones 2 and A. T. Raftery I
1Department of Surgery, The Royal Hallamshire Hospital, Sheffield, U.K. and 2Department of Surgery, Rotherham District General Hospital, Rotherham, U.K. This paper reports on our experience of vascular insufficiencyfollowing accidental intra-arterial injection in drug addicts and discusses possible treatment options and pathophysiology. Key Words: Drug abuse; Drug addiction; Injection intra-arterial).
Introduction Inadvertent intra-arterial injection of drugs is a rare but well-recognised complication of anaesthetic practice. 1-3 Such an event can cause severe tissue necrosis and gangrene, although the exact mechanism by which this produces such a dramatic effect is obscure. 4 With the increasing prevalence of drug addiction, accidental intra-arterial injection is being seen in this group of patients. A variety of substances may be injected, and complications arising from this can be difficult to treat. We report our experience of five instances of inadvertent intra-arterial injection in drug addicts, and_ discuss the treatment options and pathophysiology.
Case Reports
Case 1 In December 1987 a 26-year-old male drug addict presented as an emergency, l h following accidental injection of his left radial artery at the wrist with a suspension of crushed temazepam, codeine phosphate and diazepam tablets, which had been dissolved in tap water. He complained of immediate severe pain in the hand which on admission was ischaemic, with cyanosis and anaesthesia of all Please address all correspondence to: J. C. Cooper, RoyalHallamshire Hospital, Glossup Road, Sheffield,U.K. 0950-821X/92/040430+04 $03.00/0© 1992Grune & StrattonLtd.
fingers. He had normal brachial and ulnar pulses, and a weak radial pulse which became impalpable shortly after admission. An intravenous (i.v.) infusion of prostacyclin was commenced in combination with a stellate ganglion block, but the hand remained ischaemic. An arteriogram revealed an occluded radial artery from its origin, patent ulnar and interosseous arteries to the wrist and absent digital arteries with sluggish flow in the palm. An intraarterial infusion of streptokinase was commenced and given for 24h without improvement. Seventytwo hours following injection the patient became toxic, and the hand and forearm remained ischaemic and became oedematous. An X-ray of the forearm revealed gas in the subcutaneous tissues and an above-elbow amputation was carried out following which the patient made a good recovery. Bacteriology of the muscle taken from the hand and forearm revealed Clostridium perfringens. Histologically the radial and digital arteries were found to be thrombosed and to contain particulate foreign body material. In addition there was widespread tissue necrosis with Gram-positive cocci in the tissues. In September 1989 the same patient re-presented I h after accidental injection of his right femoral artery at the groin with a suspension of crushed triazolam tablets dissolved in tap water. He complained of severe pain in his thigh and leg which was cold and mottled. All peripheral pulses were initially palpable. He was commenced on i.v. heparin and subsequently prostacyclin, but within 12 h the leg had become very tense and swollen, and remained cyanosed. He
Accidental Intra-arterial Injection
underwent thigh and leg fasciotomies but this failed to improve the situation. His general condition deteriorated and he became very toxic and developed acute renal failure requiring haemodialysis. Thirty-six hours following admission he underwent emergency disarticulation of the left leg through the hip, from which he recovered slowly. Histology revealed extensive vascular thrombosis secondary to occlusion of the small arteries with refractive foreign material and patchy myonecrosis.
Case 2
In May 1988 a 34-year-old male drug addict presented 3 h following inadvertent injection of his right radical artery at the wrist with a solution of 150 mg of cyclizine. He had developed severe pain in his hand and fingers, and on admission the radial three digits were very painful, pale and cool with reduced sensation. His radial and ulnar pulses were both palpable. He was treated with i.v. heparin, analgesia and antibiotics. The radial three fingers remained acutely painful and swollen for several days, but this subsequently settled and the circulation improved. The tips of the thumb and index finger remained tender for several weeks but amputation was avoided.
Case 3
In October 1989 a 31-year-old female drug addict presented l h after accidental injection of her left radial artery in the anatomical snuff box with a suspension of five crushed DF118 tablets dissolved in 5ml of boiled tap water. She complained of immediate severe burning pain in the left hand and forearm which was ischaemic with cyanotic mottling to just proximal to the elbow. All major pulses were palpable. An urgent arteriogram revealed patent brachial, ulnar and radial arteries, but occlusion of the superficial and deep palmar arch arteries and no filling of the digital arteries. She was commenced on intra-arterial praxilene for 24 h and i.v. heparin, with some improvement of the circulation to her forearm, but the hand and in particular the fingers remained very ischaemic. The following day a left cervical sympathectomy was performed with some relief of the pain and improvement in the circulation of the hand. Intravenous heparin and praxilene were continued, and over the next few days she developed dry gangrene of the finger tips and subsequently, ampu-
431
tation through the proximal phalanges of all digits was performed.
Case 4
In January 1989 a 24-year-old male drug addict presented 36 h following accidental injection of his right femoral artery at the groin with a solution of methadone. On admission his foot was cold, cyanosed, painful and numb, and the calf was very swollen and tense. There were no palpable pulse below the femoral artery. An arteriogram revealed normal femoral and popliteal arteries, but poor flow in the tibial vessels. Open fasciotomies of the leg were performed, and the following day the foot became warm and pink with palpable pulses. Apart from a transient period of acute renal failure and myoglobinuria, the patient made a full recovery.
Discussion
The true incidence of accidental intra-arterial injection in drug addicts in the U.K. is unknown, but with the prevalence of drug addiction in recent years it would seem likely that it is on the increase. Certainly evidence from North America suggests the problem is becoming more common, s The covert nature of illicit drug administration means, of course, that only those addicts who develop the most severe complications are likely to seek medical help; we believe, however, that because they often use impure substances, 6 ischaemic complications are likely to occur and bring the patients promptly to the physician. In anaesthetic practice the incidence of intra-arterial injection has been variously estimated from i in 8000 to I in 55 000. 7 The most common agent reported in this situation is thiopentone, 2"3"7'8 although other drugs have been shown to produce ischaemic complications.9' 10 Exactly w h y medications which can be given safely i.v. produce catastrophic results when injected intra-arterially is not entirely clear, but several theories have been suggested based on clinical and experimental data. Burn 2"11 proposed that vasoconstriction due to the release of noradrenalin from the arterial wall was the main factor. It has been shown, however, by Kinmouth and Shepherd 12 that although thiopentone can produce experimental vasoconstriction its effect is short lived, and thereafter there is a rapid return to normal or even vasodiEur J VascSurg Vol 6, July1992
432
J.C. Cooper et al.
latation. These workers, supported by others, 4"13 attributed more significance to primary endothelial arteriolar damage distal to the site of injection, leading to necrosis of the arteriolar wall and then thrombosis. A criticism of this theory, however, is that thrombosis is probably too slow a process to account for the suddenness of the onset of symptoms, and Waters 3 proposed the formation of insoluble drug crystals. He showed experimentally that when a solution of sodium thiopentone was mixed with arterial blood it formed a precipitate of insoluble crystals, which in part was due to rapid pH changes and the formation of acid thiopentone. On the basis of this evidence, he suggested that the crystals caused an immediate mechanical arteriolar blockage which accounted for the rapid onset of symptoms. In addition the crystals provoked a release of noradrenalin from the arteriolar wall. When both the mechanical and humoral factors operated for long enough, stagnation of blood occurred leading to arteriolar thrombosis which then spread in a retrograde fashion to the main arteries. This theory is supported by our own experience of intra-arterial injection, not of crystals but of a particulate suspension, which may have similar effects on the arterioles. Immediate ischaemia followed by gangrene was a universal complication when a suspension was injected, due to particulate micro-emboli lodging in the arterioles. Interestingly, although the cases showed signs of ischaemia, all had palpable major pulses at the time of presentation, presumably because retrograde thrombosis had not yet occurred. Further proof that particulate matter was injected came from the histology from case 1, where birefringent particles were seen in the digital arteries. By contrast, when pure solutions of cyclizine and methadone were used in cases 2 and 4, symptoms developed rather more gradually and a relatively favourable outcome was achieved without amputation. We must assume in both these cases that cyclizine and methadone do not precipitate out in the arterial blood, and hence symptoms were mainly due to spasm and oedema which was relatively short lived. It may be inferred that the commonly injected substances (e.g. morphine) do not precipitate either, as few cases of serious complications following their administration have been encountered. If this mechanism is indeed true, it would explain the difficulties encountered by ourselves and others in the treatment of this condition when a suspension is injected. Various treatments have previously been recommended. These include vasodilators in combination with antibiotics, although Eur J Vasc Surg Vol 6, July 1992
whether this avoids amputation is doubtful. Kinmouth and Shepherd 12 showed experimentally that the incidence of gangrene in rabbits' ears following injection of thiopentone could be reduced by sympathectomy and heparinisation. Fasciotomy has been recommended when swelling and spasm is present, s This proved useful in case 4 when a solution was injected, and we would advocate its use in this situation. Intermittent positive pressure is claimed by other workers 14 to reduce the need for fasciotomy and promote the return of circulation. From our limited experience and that of others including a study from North America s it would seem that no single treatment is of particular value when a suspension has been injected. This is perhaps not surprising as none of the measures attack the root of the problem, i.e. dislodgement of micro-emboli from the small vessels. What is needed is a means of mechanically dislodging the emboli or dissolving them, and at present no such treatment is available. We would, however, recommend the following measures in such cases presenting with ischaemia following intra-arterial injection of a suspension of particulate matter. Antibiotics should be commenced immediately to reduce the risk of gas gangrene, and sympathectomy, either chemical or operative, may dilate up the arteriolar bed, theoretically allowing the precipitate to lodge more distally. (As an alternative systemic vasodilator therapy could be used). In addition, we would recommend i.v. anti-coagulation in an attempt to reduce retrograde thrombosis, and fasciotomy should certainly be considered if considerable swelling is present. We believe, nevertheless, that if a suspension, or a solution producing micro-emboli has been injected, distal gangrene may unavoidably develop whatever treatment is given and amputation sadly become necessary.
Acknowledgement We wish to thank Mrs C. Bagshaw for typing the manuscript.
References 1 BRowN SS, MORRELLL, DUNDEEJW. Intra-arterial barbiturates. Br ] Anaesth 1968; 40: 13-19. 2 BURN JH. Why thiopentone injected into an artery may cause gangrene. Br Med ] 1960; 2: 414-416. 3 WATERSDJ. Intra-arterial thiopentone. Anaesthesia 1966; 2: 346356.
Accidental Intra-arterial Injection
4 ENGLERHS, FREEMAN RA, KANAVAGECCB, OGDEN LL, MORETZ WH. Production of gangrene extravasaties by intra-arterial injections. Am Surg 1964; 30: 602-607. 5 BERGNERR, BENITEZ P. Surgical emergencies from intravascular injection of drugs. In: BERGANJJ, YAO JST, eds. Vascular Surgical Emergencies. London: Grune & Stratton, 1987; 309-325. 6 HAWKINSLG, LlSCHER CG, SWEENEYM. The main line accidental intra-arterial drug injection. Clin Orthop 1973; 94: 268-274. 7 COHEN SM. Accidental intra-arterial injection of drugs. Lancet 1948; 2: 361-371. 8 STONE HH, DONNELLYCC. The accidental intra-arterial injection of thiopentone. Anaesthesia 1961; 22: 995-1006. 9 KING Iq, HAWTOFDB. Accidental intra-arterial injection of ether. JAMA 1963; 184: 241-242.
433
10 BATIST G. Gangrene of the arm after intravenous injection of 'chlorpromazine. Rass Cliniosci 1960; 36: 113-114. 11 BURN JH, HOBBS R. Lancet 1959; 1: 1112-1114. 12 KINMOUTH BJ, SHEPHERD RC. Accidental injection of thiopentone into arteries. Br Med J 1959; 2: 914-916. 13 HAGER DL, WILSON JN. Gangrene of the hand following intraarterial injection. Arch Surg 1967; 94: 86-89. 14 ENGLERHS, PURVISJG, KANAVAGECCB, OGDENLL, FREEMANBS, MORITZ WH. Gangrene extremities resulting from intra-arterial injections. Arch Surg 1967; 94: 644-651.
Accepted 7 November 1990
Eur J Vasc Surg Vol 6, July 1992
