Pathogenesis of gangrene following intra-arterial injection of drugs: a new hypothesis.

We have demonstrated the toxicity of diazepam and the safety of ketamine hydrochloride following intra-arterial injection in an anaesthetized animal model. The pathogenesis of gangrene following intra-arterial injection of drugs is unclear. Clinical reports and this experiment suggest that it only follows injection of highly membrane-soluble drugs. Early swelling and disruption of capillary endothelial cells were demonstrated after intra-arterial injection of diazepam and thiopentone. We believe that a theory of pathogenesis based on this finding is consistent not only with our experimental findings, but with known in vitro effects of membrane soluble drugs on cell membranes and the clinical features following intra-arterial injections in both human subjects and in animals.     

Fingers necrosis after an accidental intra-arterial injection of flucloxacilline: case report

Accidental intra-arterial injection of drugs is rare in pediatric patients. It is a source of considerable morbidity. Vessel proximity, aberrant vasculature, difficult procedures, and clerical errors can contribute to accidental intra-arterial injection. We report a case of a 7-year-old girl who had an accidental intra-arterial injection of 500 mg of floxacillin in her right elbow for open wound of the index. Initial signs and symptoms consisted of intense forearm pain and cyanosis. Two to 3 hours later, discoloration and nail bed pallor became evident, with no radial pulse. Rapid development of signs of acute ischemia prompted urgent brachial artery embolectomy and exploration and forearm fasciotomy. Postoperative heparin was administered. Postoperatively gangrene of the five fingers of the right hand developed. We present a comprehensive review of literature, highlighting available information on symptoms, pathogenesis, sequelae and management strategies for accidental intra-arterial injection. We believe that all physicians and ancillary personnel who administer intravenous therapy should be aware of this serious risk.     

Ischaemia following selfadministered intra-arterial injection of methylphenidate and diamorphine

A patient presented with a painful, oedematous, cyanosed hand having injected a solution of diamorphine and methylphenidate into his radial artery. Treatment was started with heparin and vasodilators. Benefit from this was limited and a course of intra-arterial urokinase was instituted. This gave almost total resolution of the injury. The mechanisms producing ischaemia following intra-arterial injection of drugs of abuse and possible treatment are discussed.     

Gangrene of the hand and forearm after inadvertent intra-arterial injection of pyrazole. A case report

A case of gangrene of the hand following inadvertent intra-arterial injection of a pyrazole derivative (Tomanol) is presented. Gangrene of the hand and superficial sloughing of the distal arm necessitated a forearm amputation. Because of the serious sequelae, precautions must be taken to avoid inadvertent intra-arterial injections and due consideration must be given to the anatomical variation of the brachial artery and its branches in the cubital fossa.     

Digital gangrene after accidental intra-arterial injection of phenytoin (epanutin).

A case is described in which inadvertent intra-arterial injection of phenytoin led to digital gangrene, with arteriography showing occlusion of the digital arteries, necessitating amputation of fingers. The high alkalinity of phenytoin is strongly irritant to vessel walls. Intravenous injection of phenytoin should be given only with great care and in emergencies, preferably avoiding the cubital fossa.     

Pulmonary embolization of microcrystalline cellulose in a lung transplant recipient.

Intravenous injection of drugs that contain insoluble foreign material can lead to pulmonary embolization of the material and can have devastating results, including pulmonary hypertension and death. Most cases are detected after the onset of extensive, irreversible damage, precluding potentially life-saving intervention, or are detected at autopsy. We report here a case of microcrystalline cellulose embolization in a lung transplant recipient detected at routine transbronchial biopsy, and we describe the circumstances associated with the development of this condition and its clinical outcome.     

Relief of postoperative pain by ibuprofen: a report of two studies

The value of ibuprofen (Motrin) as an analgesic was assessed in two consecutive studies in 425 patients with postherniorrhaphy pain. In the first study, 400 mg ibuprofen proved superior to placebo and as effective as one tablet of a compound containing 375 mg of acetylsalicylic acid, 30 mg caffeine and 8 mg codeine (ACC-8). In the second study, the analgesic effectiveness of 400 mg of ibuprofen was intermediate between that of two tablets of ACC-8 and one tablet of ACC-30 (a compound containing 375 mg ASA, 30 mg caffeine and 30 mg codeine). The side effects of all drugs were negligible. Ibuprofen should be a suitable alternative analgesic in postoperative pain of this type.     

Misoprostol associated refractile material in fetal and placental tissues after medical termination of pregnancy

Misoprostol is a synthetic prostaglandin analog administered vaginally to induce labor for intrauterine death or termination of pregnancy for congenital abnormalities. We encountered a case of misoprostol induction of labor at 14 weeks of gestation for fetal acrania associated with amniotic bands. Histology demonstrated abundant deposits of refractile material appearing to be of vegetable fiber origin on the maternal surface of the fetal membranes. Misoprostol tablet scrapings had a similar microscopic appearance. Ten additional placentas from cases of misoprostol induction of labor between 16 and 18 weeks of gestation were examined and half were found to contain such deposits. No deposits were seen in cases between 15 and 18 weeks of gestation where misoprostol was not used. We attribute the refractile material to a nonmedicinal ingredient, microcrystalline cellulose, in the misoprostol tablet preparation. This study demonstrates that vaginal administration of misoprostol tablets can be detected microscopically in at least half of cases and may have a florid appearance simulating a potential causative factor of fetal malformation. Despite the large amounts of microcrystalline cellulose and its apparent embedding in placental tissue, the misoprostol in our index case was unlikely to have caused the amniotic bands and the resulting cranial abnormality.     

Localized gangrene of the scrotum and penis: a complication of heroin injection into the femoral vessels

Long-term intravenous heroin abusers have problems of vascular access. After the accessible sites are sclerosed, the neck, axillae and groins are then used frequently. We report on 3 heroin abusers who presented with localized gangrene of the genitalia after injection into the femoral vessels. We postulate that the pathophysiology of this entity is related to arterial embolization of particulate matter into the microcirculation of the genitalia, which causes arterial thrombosis leading to localized gangrene. Of the 3 patients 2 were treated with local excision, débridement and primary closure. A fourth addict who injected heroin directly into the scrotum and perineum, presented with Fournier's gangrene, a completely different, more lethal entity.     

A double-blind comparison of codeine and morphine for postoperative analgesia following intracranial surgery

Codeine and morphine were compared in a double-blind study of postoperative analgesia in 40 patients after intracranial neurosurgery. Eighteen patients received codeine phosphate 60 mg and 18 morphine sulphate 10 mg, both by intramuscular injection; 4 patients (10%) required no analgesia. Both drugs provided analgesia within 20 min of injection but morphine was more effective than codeine beyond 60 min (p = 0.01). Fewer doses of morphine than codeine were required (p = 0.003). Nine patients requested one dose of morphine and 9 two doses. Seven patients required three doses of codeine and 1 patient required four doses. Neither drug caused respiratory depression, sedation, pupillary constriction or unwanted cardiovascular effects. We conclude that, in the doses used, morphine is a safe alternative to codeine for analgesia after neurosurgery and has a more persistent action.     

Deleterious effect of urokinase used to treat experimental intra-arterial thiopental injection injuries.

Inadvertent arterial drug injections continue to be an important source of morbidity. Although the clinical picture of thiopental injection has been well defined over the past 50 years, there is still much controversy concerning pathophysiology and treatment regimen. Recently, a case report showed the efficacy of urokinase in treating this problem. The current study used the reliable ear model to study more closely this phenomenon. Rabbits were divided into four groups. Ears in Group 1 rabbits (n = 10) received an intra-arterial thiopental (15 mg/kg) injection. Group 2 rabbits (n = 10) received thiopental followed by a 1-ml saline injection 15 minutes later. Group 3 rabbits (n = 10) received thiopental followed by 50,000 U of urokinase. Finally, Group 4 rabbits (n = 4) received an intra-arterial injection of saline alone. Necrosis was evaluated 2 weeks later and expressed as a percentage. Student's t tests were used to evaluate data significance. Results: Group 1 (thiopental alone) and Group 2 (thiopental and saline) rabbits had significantly more necrosis than Group 4 (saline alone) rabbits, 21.2% and 17.5% versus 0% (p less than 0.001 for both). Group 3 (thiopental and urokinase) rabbits had significantly more necrosis (46.5%) than Groups 1 and 2 rabbits (p less than 0.001 for both). Conclusion: From this study, we found that treatment of intra-arterial thiopental injection injuries with urokinase was of no benefit, but more importantly, it increased tissue necrosis by approximately 100%. Clinical use of this treatment is to be discouraged until underlying mechanisms are better defined.     

Effect of low dose intra-arterial reserpine on vascular wall norepinephrine content.

A number of reports in recent years have indicated that the administration of low dose intra-arterial reserpine has resulted in significant clinical improvement in patients with symptomatic vasospasm, with the benefits presumably resulting from regional vascular wall norepinephrine depletion with resultant vasodilatation. However, to date, there has been no evidence that such low dose reserpine actually alters vascular wall norepinephrine content. This study was performed to determine both regional and systemic effects of low dose intra-arterial reserpine on vascular-wall norepinephrine content, and the duration of any alterations. Twenty-four mongrel dogs had vascular segments excised and assayed for norepinephrine content, before and for up to 4 weeks following a single injection of reserpine, 0.01 mgm/kg, into one femoral artery. The results indicate a pronounced norepinephrine depletion in the injected femoral arterial system, with the reduction persisting for 2-4 weeks, at which time complete norepinephrine recovery occurred. The visceral vessels sampled also showed considerable norepinephrine depletion, indicating systemic spill-over of the drug from the injected peripheral arterial tree. The visceral vessels, however, showed maximal depletion at 24 hours, with recovery by 7 days.     

Haemodynamic effects of intra-arterial and intravenous administration of prostaglandin E1 in patients with peripheral arterial disease

The purpose of this study was to compare the haemodynamic effects of intra-arterial and intravenous prostaglandin E1 (PGE1) both injected and infused into ischaemic legs. Continuous intra-arterial infusion of PGE1 induced a significantly greater increase in skin temperature and blood flow than did intravenous drip infusion. Furthermore, intra-arterial infusion caused no steal phenomenon in the toe as indicated by skin temperature. On the other hand, toe skin temperature decreased during intravenous drip in 33 per cent of the legs tested. Continuous intravenous infusion also produced a significantly greater increase in toe skin temperature than did brief intravenous drip. In three of ten ulcers healed by continuous intra-arterial infusion, no definitive effect was obtained from continuous intravenous infusion even when it was repeated up to three times before continuous intra-arterial infusion. Intra-arterial injection of PGE1 caused no significant increase in toe skin temperature.     

Intratumoral arteriovenous shunting in malignant gliomas

OBJECTIVE: Intratumoral arteriovenous shunting in glioblastomas has been suspected but neither proven nor quantified. METHODS: Using a previously described technique of selective intra-arterial intratumoral injection of 99mTc-labeled microparticles (macroaggregated albumin), we measured the amount of radioactivity, by cerebral and pulmonary scintigraphy, in seven patients with malignant gliomas (six with glioblastomas and one with an anaplastic oligodendroglioma). The pulmonary shunt index was calculated as a percentage from the pulmonary/pulmonary plus cerebral radioactivity ratio. RESULTS: The results revealed a mean pulmonary shunt index of 67% (range, 47-89%), indicating that most of the microparticles injected into the tumor via the arterial route bypassed the tumor and reached the lungs. The measured arteriovenous shunting was greater when the injection was performed in an artery exclusively perfusing the tumor. CONCLUSION: Important intratumoral arteriovenous shunting exists in glioblastomas. The potential consequences of this finding for intra-arterial treatment strategies are discussed.     

某皮肤病医院三批带量采购药品完成情况

目的 分析我院3批集采药品的执行情况，为进一步完善国家集采药品工作提供参考。方法 利 用医院数据库统计、分析已完成集采的前3批集采药品的采购量、计算限定日费用（DDC）以及带量采 购药品执行前后DDC降幅。结果 前3批次签约16个常规品种，5个品种未完成合同签约量；3个品种DDC 降幅＜20%，分别为盐酸右美托咪定注射液，非那雄胺片，碳酸氢钠片；8个品种DDC降幅＞80%分别为 阿莫西林胶囊、阿奇霉素胶囊、氟康唑片、盐酸莫西沙星片、盐酸左西替利嗪片、克拉霉素片、盐酸西 替利嗪片、地氯雷他定片。结论 本院在落实国家集采药品的相关制度和工作方面还需积极努力，3批带 量采购的药品以低廉的价格和较高的质量切实提高了患者用药的经济性和可及性。     

Intra-arterial chemotherapy of infiltrative bladder carcinoma

Twenty patients with untreated invasive high stage or high grade transitional cell carcinoma of the bladder have been treated by bilateral intra-arterial hypogastric injection of adriamycin. A total of 160 mg of adriamycin were injected during the procedure which was repeated once 3-4 weeks later. Eleven patients received two full courses of chemotherapy. In 4 patients, complete response with disappearance of all tumoral lesions was observed and in 1 patient, partial tumor regression was apparent. One patient died from pulmonary disease. Five patients received only a partial treatment because of technical difficulties, and selective catheterization was impossible in 4 because of severe arteriosclerotic lesions. No response was seen in those cases. Although this new therapeutic modality remains to be fully evaluated, preliminary results appear most encouraging since intra-arterial chemotherapy can be used safely and is effective in patients with invasive bladder carcinoma.     

Gangrene of the toes with palpable peripheral pulses.

Thirty-five patients with gangrene or pregangrene of the feed associated with palpable peripheral pulses have been treated with the platelet suppressive drugs aspirin and dipyridamole. Sulphinpyrazone was substituted for two patients who could not tolerate aspirin. Complete reversal of the signs and symptoms occurred in more than 50% of the treated patients. Recurrence of pain occurred in the five patients in whom antiplatelet therapy was discontinued. Reversal of symptoms was again achieved by reintroduction of the drugs. An increased incidence of spontaneous platelet aggregation and hypersensitive platelets was observed in those patients who responded to platelet suppressive therapy. These results indicate that platelet suppressive therapy is of therapeutic value in selected patients with peripheral gangrene.     

Intra-arterial regional anaesthesia for hand surgery with alkalinized 0.5% lignocaine

Intra-arterial regional anaesthesia (IARA) for hand surgery is an old, forgotten technique. One of the causes of low popularity may be a scalding sensation in the hand during intra-arterial injection of lignocaine, which may be caused by low pH of lignocaine's solution.
In this randomized, double-blind study, normal (pH 5.2-5.3) or alkalinized (pH 7.2-7.3) preservative-free 0.5% lignocaine 1.5 mg kg^-1 was injected into the radial arteries of forty adult patients to produce anaesthesia for ambulatory hand surgery.
Scalding sensation in the hand during intra-arterial injection (VAS) was less pronounced with alkalinized lignocaine ( P =0.04). The time of onset and regression of analgesia was similar in both groups. Four patients in group 1 (normal lignocaine) and six patients in group 2 (alkalinized lignocaine) needed supplemental analgesia at the start of surgery (NS). Cannulation time, operating conditions, motor blockade, surgical-, and tourniquet pain scores (VAS) and patient's acceptance were similar. Three patients (two in group 1 and one in group 2) had minor systemic adverse effects after tourniquet release (NS). Nine patients in group 1 and seven in group 2 developed minor bruises after cannulation (NS). No other sequelae of intra-arterial injections were observed.
We conclude that alkalinized 0.5% lignocaine was less painful on injection than normal lignocaine and should be preferred for intra-arterial regional anaesthesia for hand surgery.     

Inadvertent intraarterial injection of thiopentone

A case is recorded in which intra-arterial injection of thiopentone 2.5 percent was made into an aberrant branch of the radial artery at the lateral aspect of the wrist. Although the intra-arterial injection of thiopentone is a fairly uncommon accident, especially on the dorsum of the hand, nevertheless, precautions should always be taken to avoid it. These precautions should include palpating for a pulse before application of a tourniquet and after removal of the tourniquet, and checking for backflow of blood after insertion of the cannula. The anaesthetist should always have a high index of suspicion, should use a vessel which is significantly remote from any palpable pulse and should always pause after a test dose of one or two ml of thiopentone solution to ensure that the injection is not uncomfortable. Some of the anatomical abnormalities to be found in the arterial supply to the forearm and hand have been described, and the immediate and late treatment of accidental arterial injection of thiopentone has also been detailed.     

Management of thrombotic complications of invasive arterial monitoring of the upper extremity

Invasive arterial monitoring is essential intraoperative and perioperative management of vascular and cardiac patients. Complications resulting from arterial monitoring, although rare, can result in severe functional sequelae and loss of an extremity. Severe extremity ischemia and repeated thromboses in a 10-year-old male resulted from brachial arterial monitoring line. Multiple operative thrombectomies and systemic anticoagulation were unsuccessful. Limb salvage and arterial patency were achieved by saphenous vein patch angioplasty at site of arterial injury and intermittent intra-arterial streptokinase infusion placed into a natural side branch of the saphenous vein segment. Although many complications may result from arterial monitoring, the most serious is arterial thrombosis with impending digital or extremity gangrene. This constitutes a surgical emergency. When aggressive conventional surgical techniques alone fail to control catheter induced thrombosis, an innovative technique in combination with regional intra-arterial streptokinase therapy has been successful adjunctive measure in reestablishing microvascular patency resulting in limb salvage.