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Local skin necrosis after extravasation of doxorubicin hydrochloride (Adriamycin), a widely used chemotherapeutic agent, is a common problem in cancer patients. Even though several treatment options have been proposed for extravasation injury, there is still controversy regarding the management of such lesions. The aim of this study was to compare...
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... injections were made on the dorsal side of each rat. Intradermal doxorubicin was in- jected on the right side and subpannicular doxorubicin on the left (Fig. 1). The injection site was symmetric. Intradermal and subpan- nicular injections were made for six rats, in six different concentrations of doxorubicin (0.33, 0.5, 0.66, 1.0, 1.33, and 1.5 mg/ml). The vol- ume of the infiltration solution was 1 ml in all groups, which is the volume that can be toler- ated by the skin of the ...
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... Following intraperitoneal injection of 80 mg/kg ketamine and 10 mg/kg xylazine and preparation of the dorsal thigh regions, 1.0 mg/mL doxorubicin solutions were injected to immediate subdermal plane of both upper dorsal thigh regions to induce a standard extravasation injury as proposed by Yilmaz et al [40]. ...
... A standardized method of induction of a rat extravasation injury model with doxorubicin was developed by Yilmaz et al [40]. In their excellent work with 99 rats, not only they found out the minimum dose of doxorubicin to induce a measurable amount of tissue damage, but they also compared effectiveness of several methods in limiting the size of necrosis [40]. ...
... A standardized method of induction of a rat extravasation injury model with doxorubicin was developed by Yilmaz et al [40]. In their excellent work with 99 rats, not only they found out the minimum dose of doxorubicin to induce a measurable amount of tissue damage, but they also compared effectiveness of several methods in limiting the size of necrosis [40]. ...
Introduction: Extravasation injuries are one of the most feared complications of intravenous drug administration. The most common drugs associated with extravasation injury include chemotherapy agents and contrast media. Natural course of vesicant extravasation is discomfort, pain, swelling, inflammation, and ultimately skin ulceration. While diligence is the principle approach in prevention, immediate bed-side measures are as important in controlling the extent of tissue damage. Various options, either medical or interventional are next steps in treatment of the condition including
antidotes, volume dilution, flushing, suction, hyperbaric oxygen therapy, and surgery.
Materials and methods: 12 male Wistar albino rats were divided into two groups; one group
received fat injections following subdermal doxorubicin infiltration in their right thighs, while other group received saline injection following subdermal doxorubicin infiltration in their right thighs for dilution. Left thighs of both groups were left untreated following subdermal doxorubicin infiltration. Total area of necrosis, as well as resultant epidermal thicknesses were assessed. Histological analyses were conducted using modified Verhofstad scoring system for comparison.
Results: Mean necrotic area was significantly smaller in the fat injection group compared to other groups. Median Verhofstad score was lesser in the fat injection group as well. Median epidermal thickness, on the other hand, was greater in the fat injection group.
Conclusion: Injection of fat grafts following vesicant extravasation might be beneficial in preventing the progression of tissue damage, if employed early.
... Because anticancer drugs are more injurious to skin tissue and the resulting inflammation tends to be protracted, brief cooling or warming seems to have little effect. In addition, we followed the protocol from preliminary research in the injury of the skin with the doxorubicin administration by this experiment andchose suitable animal models [25]. Based upon these previous findings, we studied the subcutaneous leakage of 20 μl of DOX (1 μg/μl) on the panniculus carnosus muscle in the backs of mice, and examined the mechanism of the effect of 3-hrs compress application. ...
In the present study, we investigated a part of the mechanism responsible for the effects of hot and cold compresses for extravasation of doxorubicin. We injected 20 μl of doxorubicin (DOX) (1 μg/μl) subcutaneously into the dorsal area in mice and observed the resulting skin lesions macroscopically and histologically from day 1 to day 14 thereafter in groups treated with a cold pack (18-20°C) and a hot pack (38-40°C) or left untreated (control). Immunofluorescence and RT-PCR for C5a receptor (CD88), interleukin-8 receptor (IL-8RA), and transient receptor potential cation channel subfamily V member 1 (TRPV1) were also performed. Macroscopic observation showed that the area of the skin lesion was significantly smaller in the cold group than in the control group, but was significantly larger in the hot group. The neutrophil count in the lesion was significantly higher in the hot group than in the cold (3 hrs) and control groups. The numbers of inflammatory cells expressing CD88 and IL-8RA were significantly lower in the cold group than that in the other groups at almost time points and in the hot groups at later time points, respectively. The number of nerve fascicles expressing TRPV1 was higher in the hot group than in the cold group on days 1, 3 and 14. mRNA for CD88, IL-8RA and TRPV1 was detectable by reverse transcription-polymerase chain reaction in both the cold and hot pack groups. Consequently, these results suggested that the cold pack for the extravasation of DOX might reduce inflammation.
... Topical application of silver sulfadiazine and Intrasyte gel to the affected area is recommended whenever skin blistering is observed (6). More invasive methods of treatment include saline irrigation followed by suction, local administration of various vitamins and enzymes, negative pressure therapies and a combination of liposuction and saline/hyaluronidase washout (8,(13)(14)(15). Prompt fasciotomy is required if compartment syndrome is suspected. ...
In our hospital, an adverse event reporting system was initiated that alerts the plastic surgery department immediately after suspecting contrast media extravasation injury. This system is particularly important for a large volume of extravasation during power injector use. Between March 2011 and May 2015, a retrospective chart review was performed on all patients experiencing contrast media extravasation while being treated at our hospital. Immediate treatment by squeezing with multiple slit incisions was conducted for a portion of these patients. Eighty cases of extravasation were reported from approximately 218 000 computed tomography scans. The expected extravasation volume was larger than 50 ml, or severe pressure was felt on the affected limb in 23 patients. They were treated with multiple slit incisions followed by squeezing. Oedema of the affected limb disappeared after 1-2 hours after treatment, and the skin incisions healed within a week. We propose a set of guidelines for the initial management of contrast media extravasation injuries for a timely intervention. For large-volume extravasation cases, immediate management with multiple slit incisions is safe and effective in reducing the swelling quickly, preventing patient discomfort and decreasing skin and soft tissue problems.
... As for patients with superior vena cava obstruction, dissection of the bilateral axilla lymph nodes or failure to place a central catheter, peripheral intravenous line should be considered. The incidence of chemotherapy drug extravasation has been reported as 11 and 22% in children and adults, respectively (5). The vesicant potential of anthrancyclines (6), vinorelbine (7)and paclitaxel (8) extravasation have been confirmed. ...
Docetaxel is a novel type of chemotherapy drug that actively treats a number of malignant tumors. The aim of the present study was to explore the severity and natural course of tissue damage induced by docetaxel extravasation and to confirm the vesicant potential of docetaxel. Rats were selected for the establishment of the ulcer model. Different volumes and concentrations were explored to induce the skin ulcer and to confirm the optimum rational injection model. The natural course of tissue injury and pathological changes produced by docetaxel extravasation were observed by comparing to vinorelbine extravasation. A 0.4 ml volume and a 6 mg/ml concentration were the optimum rational injection model for the induction of the skin ulcer. The docetaxel extravasation induced local tissue necrosis, followed by granuloma formation and hyperpigmentation or scar formation. The severity of the injury depended on the concentration of the extravasation used in the rat model. The injury occurred on the first day following extravasation and lasted 4-6 weeks. The damage from docetaxel was weaker than vinorelbine in association with the depth and extension of necrosis. In conclusion, docetaxel extravasation can induce tissue necrosis. However, the severity of necrosis was weaker than that of vinorelbine. Docetaxel has superficial vesicant properties.
... The efficacy of the washout technique is further supported by radiographs taken before and after washout of contrast medium [11]. Controlled trials of chemotherapy extravasation in rats have shown that saline washout may reduce the area of necrotic tissue [12]. ...
... Bu durumunda tedavisinin araştırılması için hayvan modeli olarak sıçanlarda subkutan enjeksiyon modeli geliştirilmiştir. 50 ...
ara iyileşmesi oldukça karmaşık süreçler içeren ve henüz tüm detayları ile anlaşılamayan bir olgudur. Bunun yanı sıra, ortalama yaşam süresinin ve sistemik hastalıkların giderek arttığı dünyada gelişmiş ve gelişmekte olan ülkelerin sağlık bütçelerinde her geçen yıl daha fazla pay almaktadır. Bu kadar önemli bir olgu olan yara iyileşmesinin anlaşılması konusunda bilim dünyasının elindeki veriler genellikle hayvan deneylerine dayanmaktadır. Son dö-nemlerde hayvan yara modelleri dışında daha gelişmiş, ilave uzmanlıklar ve teknik gereksinimleri olan modeller de ortaya konmuştur. Model kavramı, Türk Dil Kurumu tarafından "gerçeğin aslına benzeyen bir örnek" olarak tanımlanmaktadır. Bu açıdan model gerçekle birebir aynı olmak zo-runda değildir. Bazı açılardan gerçekle ayrı düştüğü noktalar olabilmelidir. Bu açıdan bakıldığında hayvanlarda uygulanan deneysel yara modelleri de, insanda gerçekte Turkiye Klinikleri J Plast Surg-Special Topics 2015;4(1) 5 Deneysel Yara Modelleri Ö ÖZ ZE ET T Toplumlarda yaş ortalamasının artmasıyla beraber, kronik yaralar giderek daha önemli prob-leler oluşturmaktadır. Bu nedenle yara iyileşmesinin mekanizmalarını anlamaya yönelik araştır-malar ve tedavi yöntemleri geliştirme çabaları değerini hiç yitirmeden süregelmektedir. Bununla beraber, klinik kullanımdan önce hayvan modellerinde derinlemesine araştırmalar hem etik hem de pratik anlamda gereklidir. Bu derlemede amaç, deneysel yara modelleri üzerine temel farkında-lık yaratmak ve konuya derinlemesine eğilmek isteyen araştırmacılara başlangıç noktası oluştura-bilmektir. Deneysel yara modellerinin tamamını burada özetlemek mümkün değil, gerekli de değildir. Bir yara modelinde çalışılmak isteniyorsa, ideal hayvanı, ideal modeli konusunda başlan-gıç düzeyinde fikir sahibi olabilmek bu yazının amacıdır. A An na ah ht ta ar r K Ke el li im me el le er r: : Hayvan modelleri; yara iyileşmesi A AB BS ST TR RA AC CT T Chronic wounds are one of the main problems and its significance is increasing as the population ages. This leads to efforts to understand the mechanisms of wound healing and develop treatment methods. Preclinical studies to evaluate the effects of treatment attempts before its clinical use are both ethically and practically necessary. The aim of the review is to arouse basic ideas on wound healing models and provide a base for the researchers aiming to dig deep into the wound healing research. It is not feasible and also necessary to give the pertinent knowledge in a few pages. However, one should have a brief idea about which model to study, what animal to use in the ideal basis after reading this review.
... e) Miscellaneous drugs: This group includes drugs with low level of evidence in the management of extravasation of anthracycline. These drugs have shown efficacy in experimental animals only, and include vitamin C 34,35 , and E 36-59 , heparin fraction 41 , melatonin 42 , hyperbaric oxygen 43 . Scuderi et al. 44 have reported local injection of saline (20-90 ml) with occlusive topical application of corticosteroid to avoid skin necrosis. ...
... Çeşitli kemoteropötik ajan ekstravazasyonunda çok sayıda topikal antidotlar önerilmiştir. Dimetil sulfokside (8,9) lokal tokoferol (10), bikarbonat (11,12), hyalüronidaz (13,14), heparin (14), beta-adrenerjik ajanlar (8,15) ve hasar yapan maddenin etkisini azaltmak için mümkün olan en kısa zamanda doku içerisindeki maddenin nötralize edilmesi veya seyreltilmesi amacıyla lezyon bölgesine serum fizyolojik, granülosit koloni stimüle faktör, granülosit-monosit koloni stimüle faktör, enjeksiyonunun faydalı olduğuna dair çalışmalar mevcuttur (16)(17)(18)(19)(20). Bunların çoğu lokal enflamasyonun azaltılması ve nötralizasyon vezikan ajanların dilüsyonu içindir. ...
... Such therapies have ranged from immediate irrigation with saline followed by suction, to local administration of various vitamins and enzymes into the skin, to negative pressure therapies. 5,10,11 . These invasive therapies for extravasation have not been compared to conservative management in a randomized controlled trial. ...
Extravasation of CT scan contrast media into upper extremity subcutaneous tissue is a relatively frequent complication of injection. Potential sequelae of extravasation include compartment syndrome, skin sloughing, and necrosis. Many institutions institute protocols requiring inpatient plastic surgery consultations immediately following extravasation injury to the upper extremity. We hypothesize that conversion to non-ionic contrast media for contrast CT studies has greatly reduced the incidence of severe extravasation injuries, and may alleviate the need for routine hand surgery consultations.
Records from 102 consecutive CT contrast media extravasation injuries were identified. Data acquired from a single institution included type and amount of contrast extravasated, anatomic location, post-procedural clinical symptoms, whether consult was obtained, and final recommendations and outcome.
In 102 consecutive cases, immediate surgical therapy was necessary in 0. Non-ionic medium was used in 94% of these cases, and ionic dye was used in 6%. Extravasation of less than 100 cc occurred in 90%, and only 10% were greater. Plastic surgery consultation was immediately obtained in 42% of cases. Factors prompting consultation included extravasation >30 cc, and the presence of erythema or induration. Trends for consultation remained without discernable pattern when patients were stratified by age, amount of extravasate, or anatomic location. Conservative management was recommended in all cases. This included elevation of the extremity, frequent pulse and sensation exams, local message, and temporary splinting. There were no secondary complications requiring surgical intervention.
Extravasation of non-ionic CT contrast media appears to be innocuous and can be treated with conservative therapy. Plastic surgery consultation should be obtained when there are obvious signs of skin and soft tissue compromise or symptoms of compartment syndrome.
... Maceration of the skin and subsequent necrosis have been reported as complications of this therapy (4). Yilmaz et al described a successful saline flushout method in their experimental study in rats (10). In this technique a blunt-ended canula with side holes is used to inject saline (11). ...
Aim: Parenteral alimentation fluids containing calcium are widely used to treat sick neonates and children. Extravasation of calcium presents with local swelling, erythema, blistering and progresses to skin necrosis and skin loss. Several treatment modalities including hyperbaric oxygen therapy have been used for extravasation injuries. The role of hyperbaric oxygen therapy on extravasation injuries was investigated in this study by an experimental rat model based on facilitating effect of hyperbaric oxygen on wound healing. Methods: After shaving the dorsal side of 16 female Wistar rats, 1 ml of calcium chloride were injected intradermally. The rats were divided into two groups as control and hyperbaric oxygen. The control group received no treatment while the hyperbaric oxygen group received hyperbaric oxygen therapy for 7 days after injection. At the end of seventh day skin biopsy including all necrotic tissue and surrounding healthy tissue were obtained and histopathologic examination was performed for control and hyperbaric oxygen groups. Results: Hyperbaric oxygen group showed a statistically significant preservation of epidermis and dermis with minimal necrosing findings of skin injury. Conclusion: Although further research is required to develop management guidelines, we concluded that in this experimental study, hyperbaric oxygen therapy prevents dermal injury and may decrease the morbidity associated with calcium chloride extravasation injury.
