Prevention of tissue necrosis due to accidental extravasation of cytostatic drugs by a conservative approach

Summary The purpose of the present study was to evaluate comparatively the effectiveness of a conservative approach to treatment, using two therapeutic schedules (with and without sodium thiosulfate (ST), so as to minimize necrosis due to drug extravasation and to avoid the need for reconstructive surgery. The 63 patients entered into this study were seperated into two groups; these in group A were treated with hydrocortisone and dexamethasone, and these in group B received the combination plus ST. In both groups, the drugs that had extravasated included doxorubicin, epirubicin, vinblastine, mitomycin C. The healing time varied with the different drugs used and was proportional to the extent of extravasation and to the time at which therapy was begun. The mean healing time for group B, which received ST was about half that for group A, which did not. We conclude that the application of conservative measures during chemotherapy may prevent tissue necrosis due to drug extravasation and the subsequent need for reconstructive surgery. The administration of ST can help in the achievement of this goal.     

Extravasation of liposomal doxorubicin induces irritant reaction without vesicant injury

Anthracycline extravasation is an uncommon but very serious complication. Very few data are available in the literature concerning the consequences and the management of extravasation of liposomal doxorubicin. This report describes the cases of two patients with liposomal doxorubicin extravasation who developed irritant reaction without vesicant or necrotic lesions. It is concordant with other cases described in the literature and suggests that extravasation of liposomal doxorubicin can be relatively well tolerated. The process applied to extravasations of irritant and non-vesicant agents could be used to manage extravasations of liposomal doxorubicin.     

Topical dimethylsulfoxide may prevent tissue damage from anthracycline extravasation

Summary The optimal management of anthracycline extravasation remains unclear. Traditional topical measures to reduce local tissue damage, including corticosteroids, sodium bicarbonate, and ice applications, have not consistently demonstrated beneficial effects. This report describes our experience with four adult patients who suffered anthracycline extravasation and were treated with a regimen of ice, local glucocorticoid injection, and dimethylsulfoxide (DMSO) 55%–99% applied topically every 2–4h after extravasation for a minimum of 3 days. In all four cases, pain and erythema resolved within 2 days; in no case did tissue necrosis or skin ulceration occur. Topical DMSO is a safe, inexpensive agent that appears to reduce the risk of anthracycline-induced tissue damage. Further studies are needed to determine the optimal dose and schedule of DMSO application and to assess its efficacy in extravasation injuries from other vesicants.     

Autologous fat transfer in reconstructive breast surgery: indications, technique and results.

AIMS: Reconstructive techniques using flaps to preserve the enveloping skin, and even the nipple areolar complex where there is no neoplastic infiltration, have led to vast improvements in the results of reconstructive breast surgery. To further improve the cosmetic outcome, we have applied the technique of autologous fat transfer or lipoinjection, which has proven very successful in cosmetic surgery, to reconstructive breast surgery, and to the treatment of certain cosmetic sequelae of conservative breast treatment. We report our findings. METHODS: From September 2001 to September 2005, 74 autologous fat transfers were undertaken in 69 patients, with 5 patients receiving injections in both breasts, to improve the cosmetic appearance through resurfacing and to repair certain sequelae of conservative breast treatment. Pre- and postoperative imaging, including MRI, were undertaken to monitor the viability of the fat grafts and detect any suspicious lesions; no suspect lesions were detected either pre- or postoperatively. RESULTS: We did not undertake overcorrection, which creates irregularities of surface or contour. Five cases of cytosteatonecrosis were reported among the 74 procedures. The mean follow-up period for the patients was 11.7 months, ranging from 1 month to 3.2 years. The panel judged improvement to be good to very good in 64 breasts (86.5%) and moderate in 10 breasts (13.5%) primarily due to lack of available adipose material for harvesting in these patients. CONCLUSION: Autologous fat transfer is now a routine procedure in our clinic due to its simplicity, safety, and reproducibility. It is systematically proposed to all of our patients as the final, perfecting procedure of breast reconstruction, irrespective of the technique used for the initial reconstructive procedure, but also to repair certain conservative treatments.     

Treatment of anthracycline extravasation with dexrazoxane -- clinical experience

BACKGROUND: Accidental extravasation is a severe complication when administering anthracyclines. We describe 3 cases of extravasation with 3 different anthracyclines. PATIENTS AND METHODS: One patient came from another hospital for a second opinion after an epirubicin extravasation. Only surgical debridement of the necrotic tissue was possible. The other two extravasations occurred during treatment with doxorubicin and doxorubicin- EMCH, respectively, in our department. Both patients were treated with dexrazoxane within 6 h of the event. RESULTS: The 2 patients treated with dexrazoxane recovered completely without any sequelae. CONCLUSIONS: Treatment of antracycline extravasation with dexrazoxane is potentially useful and safe.     

Zytostatikaextravasate

Extravasation of systemic chemotherapy agents is a much-feared adverse event in oncology patients. Extravasation into the soft tissues can lead to severe ulceration and functional impairment of the extremities. The incidence of extravasation reported in the literature is 0.1–6%. The proper maintenance of intravenous lines, immediate discontinuation of the infusion, application of local cooling or warming for specific extravasations, and the use of antidotes to some, to prevent the local toxic effects of the extravasated agents, are the basis of adequate management. This review focuses on the etiology, pathomechanism, and prevention of the extravasation of systemically administered chemotherapy agents and its conservative and surgical management, all with reference to the current literature available.     

Prevention of extravasation necroses as a complication following intravenous cytostatic drug therapy. Results of an open pilot study

Extravasation of some cytostatics applied i.v. can often cause local edema with skin redness, thrombophlebitis and not infrequently skin necrosis with chronic ulcera. Local treatment is usually ineffective, and so far surgical excision of ulcera is the only curative approach. Tetrachlorodecaoxygen anion complex (TCDO) has shown high activity in healing chronic leg ulcera, by increasing pO2 in hypoxic wound tissue and stimulating phagocytosis as one of anti-inflammatory processes To study the local activity of TCDO in tissue necrosis and chronic ulcera caused by cytostatic extravasation, 23 patients with local skin complications underwent local treatment with TCDO, made as isotonic water solution. Seventeen patients experienced only local edema with redness, while 6 patients showed deep chronic ulcera. All the skin changes were complications after i.v. doxorubicin, cisplatinum, dactinomycin or vinblastine application. The treatments with TCDO followed 1-3 months after ulcera appeared, while skin inflammations were treated 1-8 days after they occurred. TCDO was applied locally twice a day by impregnated cotton tissue for 4-6 weeks. Evaluable were only measurable lesions. From 17 patients with only skin inflammation 3 patients obtained complete resolution, 8 partial resolution and 6 had stable lesions. Thus, overall response was recorded in 65% of patients (11/17). In 6 patients with deep chronic ulcera a longer treatment (6 weeks) was needed, and in 5 of them the complete epithelization and resolution occurred. One patient had a partial wound healing. No side effects of treatment were observed. The effect of locally applied TCDO in chronic ulcera seems to be preferable to surgical treatment. A controlled study will show the exact therapeutic value of this new anti-inflammatory compound.     

Extravasation of chemotherapeutic agents: prevention and treatment

Most chemotherapeutic agents can cause varying degrees of local tissue injuries when extravasated. The medical treatment of extravasation is based on proper maintenance of the intravenous (IV) line and application of cold or warm compresses, plus the use of antidotes when available. Antidotes for extravasation that have been shown to be useful are sodium thiosulfate for nitrogen mustard, dimethylsulfoxide for anthracyclines and mitomycin, and hyaluronidase for the vinca alkaloids. New treatments include dexrazoxane, sargramostim, and hyperbaric oxygen for doxorubicin extravasations. Tissue damage secondary to drug infiltration occurs as a result of one of two major mechanisms: (1) the drug is absorbed by local cells in the tissue and binds to critical structures (eg, DNA, microtubules), causing cell death; and (2) the drug does not bind to cellular DNA. Damage to immediately adjacent tissue is more readily neutralized than is damage to surrounding tissue.     

Study of patients with intravenous contrast extravasation on CT studies, with radiology staff and ward staff cannulations

Introduction: Intravenous (IV) contrast extravasation is an adverse outcome of computed tomography (CT) studies. This study evaluates for any differences in rates of extravasation between radiology (radiographer) staff and ward medical staff cannulations, and secondarily by cannula size and study type. Method: A prospective study of 26 854 studies in adults between September 2004 and April 2008 accumulated 119 extravasations. Patients were divided into two groups, those cannulated by radiology staff and those cannulated by non‐radiology staff. Patients with extravasations were followed for treatment outcomes. Statistical analysis between our groups was undertaken. Results: The total extravasation rate was 0.44%. The extravasation rate for those patients cannulated by radiology staff was 0.34% (n = 11 470 cannulations) and those cannulated by non‐radiology staff was 0.52% (n = 15 384 cannulations). This was not statistically significantly different. The site where most extravasations occurred was at the elbow (71.4%). The injection rate where most extravasations occurred was in the 1–2 mL/s range (42%). No patient required surgical intervention or had any significant morbidity. Conclusion: Radiology radiographer staff can provide safe administration of IV contrast in CT scanning with low rates of extravasation. Extravasation may occur with high or low injection rates and when small or large size cannulas are used.     

Extravasation of doxorubicin from vascular access devices

An assessment was made of 36 extravasations of Adriamycin (doxorubicin) in which vascular access devices had been used. Of these, 25 (69%) were sufficiently severe to warrant removal of the device. Physical manifestations were frequently of delayed onset. Edema and/or erythema often involved extensive areas around the catheter or access device and in several cases were accompanied by pain, discomfort or paresthesia. In 20 patients (59%), spontaneous resolution without ulceration occurred in spite of occasional extravasation of large amounts of doxorubicin. Most extravasations were caused by a limited number of technical errors and equipment problems. These were equally divided by site into injection port extravasations and catheter-related extravasations (18 patients each). The two most frequent causes were needle and catheter tip dislodgements. Procedures are suggested for minimizing the opportunities for extravasation of doxorubicin administered through vascular access devices.     

Case report: topical DMSO for mitomycin-C-induced skin ulceration

Mitomycin-C is a commonly used anticancer drug for patients with advanced anal, breast, colorectal, gastric, lung, or pancreatic cancers. Mitomycin-C can cause severe necrosis and ulceration when extravasated inadvertently into skin and soft tissues following IV drug administration. Local applications of heat, ice, and common antidotes such as glucocorticosteroids and hyaluronidase or sodium thiosulfate have failed to reduce the experimental toxicity of these vesicant reactions in mice. Plastic surgery with split-thickness skin grafting may be required to palliate local pain symptoms and loss of function, although some extravasations heal without any local treatment. This brief communication summarizes two case reports of the treatment of severe mitomycin-C venous extravasations using topical applications of dimethylsulfoxide (DMSO). Although the authors' experience represents the results of DMSO interventions in only two patients, the response to treatment in both patients was so pronounced that others may find this useful in their practice.     

Preventing and managing vesicant chemotherapy extravasations

Although vesicant chemotherapy extravasations cannot be entirely prevented, the risk of extravasation can be reduced by adhering to guidelines for safe vesicant administration. These include engaging patients in extravasation-prevention efforts, thoroughly assessing patients receiving vesicants, selecting an appropriate administration site for peripheral vesicant administration, and checking for a blood return prior to and during vesicant administration. In addition, whenever an extravasation occurs or is suspected, vesicant administration must immediately cease, and the appropriate antidote or treatment needs to be promptly administered.     

Treatment of anthracycline extravasation from centrally inserted venous catheters

The treatment of accidental extravasation of anthracycline-based chemotherapy has markedly improved with the recent introduction of a systemic anti-dote, Savene. However, efficacy data on this treatment is mainly based on extravasation from peripheral catheters. This review presents data on 7 cases of Savene treatment of anthracycline extravasations from central venous catheters.     

The effect of GM-CSF (granulocyte macrophage colony stimulating factor) on doxorubicin induced tissue necrosis and wound healing

PURPOSE: The effect of GM-CSF (granulocyte macrophage-colony stimulating factor) on tissue necrosis and ulceration induced with doxorubicin extravasation was studied. MATERIALS AND METHODS: Adult Wistar-Albino rats (n=36) were used in the study. Doxorubicin (0.4mg/300 g) was applied subcutaneously to abdominal wall. In group I (n=18), half hours after doxorubicin injection, GM-CSF 6 microg/300 mg was applied subcutaneously to the same localization. In group II (n = 18) same amount of physiologic saline (0.5 ml) were given subcutaneously to the injection site (as vehicle control groups). Group II and I were examined for induration or ulceration on 7th and 21st day. After evaluating the lesions, the injection sites were excised. Hydroxyproline (5-HP) values of dry tissue samples were calculated and histopathologic examination was done. RESULTS: At day seven there were four and eight ulceration in groups I and II, while there were four and 14 ulceration in the second evaluation at day 21st (p<0.05). 5-HP values of the groups were as follows. 97.43+/-20.39 in group land 91.34+/-22.26 in group II. Although there was an increase in epithelization, eosinophil and lymphocyte infiltration and mast cell number in group I in histopathologic examinations only the increase in angiogenesis in group I was found to be statistically significant (p<0.05). CONCLUSION: It can be concluded that GM-CSF may have beneficial effect in the treatment of doxorubicin induced tissue necrosis.     

The efficacy of saline washout technique in the management of exfoliant and vesicant chemotherapy extravasation: a historical case series report

This report presents the results from a historical case series of cytotoxic drug extravasations managed by saline washout; its purpose is to assess the efficacy of the procedure based on patient outcome. Eighty‐nine patients were identified as having experienced a vesicant or exfoliant extravasation from incident reports filed over a 10‐year period, from 1 April 2001 to 31 March 2011. Outcome was measured against the need for further surgical treatment being required. Of the 89 cases assessed for efficacy of saline washout one patient experienced a wound infection, which was treated effectively with oral antibiotics. There were no other complications reported and no patients required further treatment with surgical debridement. The majority of patients had no deferral of treatment as chemotherapy could be continued in their unaffected arm immediately following saline washout procedure. For patients where cannulation in their opposite arm for continuation of treatment was not advisable chemotherapy was delayed between 3 and 7 days. Hospitalisation as a result of the extravasation or subsequent treatment was not required in any of the 89 cases. Results indicate that saline washout technique is a safe and effective management strategy for the treatment of both vesicant and exfoliant chemotherapy extravasation.     

Operative Therapie des nichtinvasiven und invasiven Mammakarzinoms

Breast-conserving surgery has become the standard procedure for local treatment of breast cancer today. Preinvasive and other nonpalpable lesions require an interdisciplinary approach with wire-guided localisation. If a larger resection is necessary, oncoplastic surgical techniques are helpful to prevent unsatisfactory cosmetic results. Primary chemotherapy has further increased the conservative options in locally advanced tumours. A variety of different reconstructive methods, including both prosthetic reconstruction and autologous flap reconstruction, can be offered to those patients who require mastectomy. Sentinel node biopsy can be done in almost half the cases of primary breast cancer. Because of the advanced surgical techniques used today, morbidity after breast surgery has been reduced, and an ongoing gain in quality of life for breast cancer patients has been achieved.     

Local microwave hyperthermi and irradiation in cancer therapy: Preliminary observations and directions for future clinical trials

This report outlines the preliminary experience at the Mallinckrodt Institute of Radiology with hyperthermia and irradiation. Twenty-nine lesions were treated with 400 rad fraction given every 72 hours (twice weekly) for a total dose of 2000 to 4000 rad followed by byperthermia (2450 M z or 915 MHz microwaves, 42.0°–43°C, 90 minutes, every 72 hours.) In addition, 6 lesions were treated with threeof 500 rad fofiowed by hypertbermia and 12 with irradiation alone (three doses of 600, 700 or 800 rad every 72 hours). In the lesions treated with 2000 to 4000 rad and heat, nine of 12 recurrent epidermoid carcinomas of the hea and neck showed complete regression (7%) and one more than 50% response. Four of five metastatic melanoma nodules showed complete regression of the tumors and one over 80% response. Of nine recurrent adenocarcinoma of the breast nodules in the chest wall treated with 3200 to 4000 rad, five lesions exhibited complete regression and two others about 80%. Four of five metastatic melanoma nodules and three soft tissue sacomas had complete tumor regression. Of the six lesions treated with 1500 red and hypertbermia, two metastatic melanomas showed comppletel regression (CR), and three tumors exhibited partial regression. Despite the fact that the majority of the patients had been previously treated with defimitive radiotherapy, the retreatment with moderate doses of irradiation and beat) has been well tolerated. Of the 35 sites treated, four (11%) developed blisters, seven (20%) erythema only, three (8%) moist desquamation and 27 (77%) dry desquamation. There has been one instance of severe necrosis of soft tissues in the upper neck, in a patient previously treated with 5000 rad and surgery. Additio ial clinical trials are warranted to assess the potential value of hyperthermia alone or combined with irradiation in the treatment of selected cancer patients.     

Zytostatikabedingte Paravasate – ein seltenes Ereignis?

Intravenous drug application is a daily activity in every hospital and medical practice. One of the major challenges for doctors and nurses is obtaining a safe intravenous line in every situation. Unfortunately complications are always possible. One of the most dangerous problems is extravasation of local toxic agents. The frequency of extravasation and the extent of tissue damage are different depending on localisation of the vein and other risk factors, such as restlessness of the patient or lymphedema of the extremity. It is essential to prevent extravasation by minimizing iatrogenic failures and by educating patients prior to application of toxic substances. If extravasation occurs the infusion has to be stopped immediately and general actions as well specific antidotes have to be administered.     

The histologic response of soft tissue sarcoma to radiation therapy

Twenty-seven patients with soft tissue sarcoma had preoperative radiotherapy, limb-sparing marginal surgical resection and whole-mount tumor histologic analysis. Incisional biopsy specimens before radiotherapy were reviewed for tumor type, grade, and extent of necrosis. Preoperative radiotherapy was given in either of two regimens: 13 patients received a mean total dose of 5250 cGy in one daily 180 to 200 cGy fractions and 14 patients a mean total dose of 4770 cGy in two daily fractions of 180 to 200 cGy separated by 4 hours. Twenty-one specimens had at least 80% necrosis or severely altered cells, a 3+ to 4+ response. Grade and size of the tumor appeared to be indicators of response to treatment rather than histologic type. Three of five patients (60%) with Grade 1, eight of 11 patients (73%) with Grade 2 lesions, and ten of 11 patients (91%) with Grade 3 tumors had 80% or greater necrosis or severely altered cells. For tumors 10 cm or less in greatest diameter, the 3+ to 4+ histologic response was seen in 12 of 14 patients (86%) whereas for lesions greater than 10 cm, this response was observed in nine of 13 patients (69%). For patients with Grade 2 or 3 soft tissue sarcoma, 13 of 14 patients (93%) treated with two fractions per day and two of four patients (50%) receiving one fraction per day exhibited significant response. All six patients treated twice daily for lesions greater than 10 cm had 3+ to 4+ histologic response compared to three of seven (43%) patients treated once per day. Therefore, grade and size of soft tissue sarcoma are important predictors of response to radiotherapy and preoperative twice daily radiotherapy may more likely permit the conservative surgical excision of sarcomas of borderline resectability.     

抗肿瘤药外渗性皮肤损伤的防治进展

抗肿瘤药外渗是化疗过程中的常见并发症之一。药物渗漏到皮下组织,可引起局部红肿、疼痛,甚至造成皮肤组织坏死,给患者带来巨大的痛苦,应引起广泛重视。应以预防为主,一旦发生药物外渗,根据不同外渗药物,立即采取相应处理,减少炎症和组织坏死。近年来,随着大量研究和临床实践不断深入,抗肿瘤药外渗的防治有了一定提高。