Patent blue V 2.5% solution for injection 2ml ampoules

Blue dyes are a common cause of perioperative hypersensitivity (POH) reactions, with studies reporting 1:300 patients having reactions ranging from localised urticaria to circulatory collapse [1]. Sentinel lymph node biopsy (SLNB) is the gold standard in early-stage breast cancer detection, using the combination of blue dye and isotope tracing with an identification rate of 98.8% [2]. The mode of sensitisation to patent blue V (PBV) is unknown as patients typically react on their first subcutaneous exposure. PBV is also used to colour products such as textiles, food and cosmetics, and exposure to PBV is almost inevitable in daily life. However, no information is available regarding potential risks of allergic reactions to PBV, through such exposure, after confirmed allergy to subcutaneous exposure. After a suspected POH reaction, it is important to refer patients for allergy investigation to identify the culprit drug and find a safe alternative [3]. The aims of this single-centre retrospective study were to identify patients investigated for suspected POH to PBV, characterise reactions, determine the proportion of patients with confirmed allergy to PBV and to evaluate the frequency of oral tolerance among patients with confirmed allergy to subcutaneously administered PBV. Data were collected from the Danish Anaesthesia Allergy Centre (DAAC) database from 2004 to 2023 and included clinical history, symptoms from the POH reaction, results of skin tests, in-vitro tests and drug provocation in 843 patients. In total, 843 patients had been investigated and 75 (8.9%) had been exposed to PBV prior to the suspected POH reaction and were included in the study. Included patients were predominantly women (n = 68, 91%, mean age: 56 years) with breast cancer. Of the 75 patients, 54 (72%) were diagnosed with PBV hypersensitivity. Symptoms occurred <30 min after injection in 30 cases (67%) and >30 min after injection in 15 cases (33%), unknown in 9 patients. Of the 21 patients testing negative to PBV, two tested positive to dicloxacillin and chlorhexidine, respectively. Of patients testing positive to PBV 28 (52%) suffered grade III reactions (modified Ring and Messmer classification [3]), meeting the criteria for anaphylaxis; 19 had grade I reactions, of which 6 had localised urticaria and 10 had generalised urticaria. Diagnosis of allergy to PBV were made by skin prick test (SPT) in concentrations of 0.25, 2.5 and 25 mg/mL and intradermal test (IDT) in concentrations of 0.025 and 0.25 mg/mL. In total, 52 out of 54 patients with proven hypersensitivity to PBV underwent titrated sublingual and oral provocation up to 30 mg of PBV. This was tolerated by all patients. The protocol used for oral challenge with PBV is shown in Figure 1. To our knowledge, this retrospective single-centre study presents the largest series of patients with PBV allergy so far and provides important information on clinical features and investigation results. It is also the first study to address oral tolerance to PBV in patients with confirmed allergy. This has important implications for patients, who do not need to avoid exposure in their daily life. This is consistent with oral tolerance being described in patients with allergy to parenteral exposure to other substances such as carboxymethylcellulose [3, 4]. This suggests differences in activation of the immune system on oral/sublingual and subcutaneous exposure, respectively. Through 20 years of data on POH reactions to PBV available in DAAC, there were no cases of cardiac arrest or permanent injury, but 52% had reactions meeting the criteria for anaphylaxis. Balancing the risk of possible adverse effects to blue dyes against the improving the diagnostic value has been debated in the literature, emphasising the relatively high risk of allergic reactions including anaphylaxis. Currently there is no consensus as some studies suggest adding PBV in SLNB is needed to increase the sensitivity of the procedure, others do not find increased sensitivity when adding PBV [2, 5]. A meta-analysis quantified the risk of anaphylaxis to various blue dyes, and it was noted that a volume <2.0 mL and intradermal injection reduced the risk of anaphylaxis. The use of PBV in patients with melanoma allows intradermal injections, while the dye is injected parenchymally and typically at a larger volume in patients with breast cancer. Melanoma patients have been shown to have a 19-fold reduced risk of blue dye induced anaphylaxis, when compared to patients with breast cancer [6]. Unfortunately, we were not able to evaluate whether dosage of PBV correlated to severity of allergic reactions as information about dosage was not available in the majority of cases. Limitations of our study includes the retrospective method and potential selection bias either due to minor localised allergic reactions to PBV being overlooked or just concluded to be due to PBV without referring for allergy investigation at DAAC. Future studies should address how patients are sensitised to PBV and why sensitisation does not lead to clinical reactions on oral exposure. In addition, studies should investigate potential risk factors for allergic reactions, such as administration route and injected volume, with an aim to reduce the incidence of these reactions. In conclusion, PBV tested positive in 72% of patients who had a POH reaction during surgery, where PBV had been administered, and it caused both localised and severe reactions. Patients with proven hypersensitivity to patent blue V tolerate oral exposure and do not need to avoid patent blue V in foods, drinks and textiles. Conception and design: L.H.G., M.K., H.M. Acquisition of data: B.B.M., L.H.G., M.K., H.M. Data analysis and interpretation of data: S.S., J.K.B., B.B.M., L.H.G. Drafting the manuscript: S.S., L.H.G. Critical revision for important intellectual content and final approval: S.S., J.K.B., B.B.M., L.H.G., M.K., H.M. The authors declare no conflicts of interest. Detailed methods and results sections are available at: https://zenodo.org/doi/10.5281/zenodo.12205275.

Abstract licence: CC BY-NC-ND

Anaphylaxis is a constant perioperative concern due to the exposure to several agents capable of inducing hypersensitivity reactions. Patent blue V (PBV), also known as Sulfan Blue, a synthetic dye used in sentinel node research in breast surgery, is responsible for 0.6% of reported anaphylactic conditions. We present a case of a 49-year-old female patient who underwent left breast tumorectomy with sentinel lymph node staging using PBV and experienced an anaphylactic reaction. We conducted a literature search through PubMed for case reports, case series, review and systematic reviews since 2005 with the keywords “anaphylaxis” and “patent blue”. We then included articles found in these publications’ reference sections. We found 12 relevant publications regarding this topic. The main findings are summarized, with information regarding the clinical presentation, management, and investigation protocol. Hypotension is the most common clinical manifestation. The presentation is usually delayed when compared with anaphylaxis from other agents and cutaneous manifestations are occasionally absent. Patients may have had previous exposure to the dye, used also as a food, clothes and drug colorant. The diagnosis of anaphylaxis in patients under sedation or general anesthesia may be difficult due to particularities of the perioperative context. According to the published literature, the presentation of the reaction is similar in most cases and a heightened clinical sense is key to address the situation appropriately. Finding the agent responsible for the allergic reaction is of paramount importance to prevent future episodes. A anafilaxia pode ocorrer durante o período perioperatório devido à exposição a diversos agentes capazes de induzir reações de hipersensibilidade. O corante Sintético Azul Patente V (APV), também conhecido como Sulfan Blue, é usado na pesquisa de linfonodo sentinela em cirurgia de mama, e é responsável por 0,6% dos eventos anafiláticos relatados. Descrevemos o caso de uma paciente de 49 anos de idade, submetida à tumorectomia de mama esquerda com estadiamento de linfonodo sentinela, em que se empregou o APV e que apresentou reação anafilática. Por meio do PubMed, pesquisamos publicações que documentavam relatos de casos, séries de casos, revisões e revisões sistemáticas desde 2005 usando as palavras-chave “anaphylaxis” e “patent blue”. Em seguida, incluímos artigos encontrados na lista de referências dessas publicações. Encontramos 12 publicações relevantes sobre o tópico. Os principais achados estão resumidos, com informações do quadro clínico, tratamento e protocolo de investigação. A hipotensão foi a manifestação clínica mais frequente. De forma geral, o quadro clínico tem início tardio quando comparado à anafilaxia por outros agentes e, ocasionalmente, as manifestações cutâneas estão ausentes. Os pacientes podem ter tido exposição prévia ao APV, que também é usado como corante de alimentos, roupas e medicamentos. O diagnóstico de anafilaxia em pacientes sob sedação ou anestesia geral pode ser difícil devido às peculiaridades do contexto perioperatório. Segundo a literatura publicada, a apresentação da reação é semelhante na maioria dos casos e um discernimento clínico aguçado é fundamental para enfrentar o evento adequadamente. Encontrar o agente responsável pela reação alérgica é essencial para a prevenção de futuros episódios.

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Natural and synthetic colorants present in food can modulate hemostasis, which includes the coagulation process and blood platelet activation. Some colorants have cardioprotective activity as well. However, the effect of genipin (a natural blue colorant) and synthetic blue colorants (including patent blue V and brilliant blue FCF) on hemostasis is not clear. In this study, we aimed to investigate the effects of three blue colorants-genipin, patent blue V, and brilliant blue FCF-on selected parameters of hemostasis in vitro. The anti- or pro-coagulant potential was assessed in human plasma by measuring the following coagulation times: thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (APTT). Moreover, we used the Total Thrombus formation Analysis System (T-TAS, PL-chip) to evaluate the anti-platelet potential of the colorants in whole blood. We also measured their effect on the adhesion of washed blood platelets to fibrinogen and collagen. Lastly, the cytotoxicity of the colorants against blood platelets was assessed based on the activity of extracellular lactate dehydrogenase (LDH). We observed that genipin (at all concentrations (1-200 µM)) did not have a significant effect on the coagulation times (PT, APTT, and TT). However, genipin at the highest concentration (200 µM) and patent blue V at the concentrations of 1 and 10 µM significantly prolonged the time of occlusion measured using the T-TAS, which demonstrated their anti-platelet activity. We also observed that genipin decreased the adhesion of platelets to fibrinogen and collagen. Only patent blue V and brilliant blue FCF significantly shortened the APTT (at the concentration of 10 µM) and TT (at concentrations of 1 and 10 µM), demonstrating pro-coagulant activity. These synthetic blue colorants also modulated the process of human blood platelet adhesion, stimulating the adhesion to fibrinogen and inhibiting the adhesion to collagen. The results demonstrate that genipin is not toxic. In addition, because of its ability to reduce blood platelet activation, genipin holds promise as a novel and valuable agent that improves the health of the cardiovascular system and reduces the risk of cardiovascular diseases. However, the mechanism of its anti-platelet activity remains unclear and requires further studies. Its in vivo activity and interaction with various anti-coagulant and anti-thrombotic drugs, including aspirin and its derivatives, should be examined as well.

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Abstract The sol-gel spin coating method, an easily applicable, low-temperature, and inexpensive method, was used to grow Patent Blue V (PBV) organic thin films placed between metal and semiconductor. Atomic force microscope images were taken to reveal the morphological structure of the resulting organic film. FTIR, NMR, and UV-Vis measurements were taken to investigate the chemical features and optical structure of the PBV molecule. Using the traditional I-V, Cheung, and Norde methods of the produced Al/PBV/p-Si diode structure, ideality factor ( n ), barrier height (Φ b ), series resistance ( R s ), and interfacial density of states ( N ss ) parameters were calculated. The differences between the results obtained with these methods arise from calculating the I-V characteristic of the methods from different regions. The ideality value of n for the produced diodes is much greater than one ( n &gt; &gt; 1). Deviating the calculated n value from 1 indicates possible mechanisms, such as generation-recombination effect, organic PBV layer, and interfacial states. It was observed that the electronic parameters of the Al/p-Si conventional junction can be controlled using an organic PBV interlayer. Graphical abstract

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Background and objective: Subpleural located pulmonary nodules are perioperatively invisible to the surgeon. Their precise identification is conventionally possible by palpation, but often at the cost of performing a thoracotomy. The aim of the study was to evaluate the success rate and feasibility of the pre-operative CT-guided marking subpleural localized nodule using a mixture of Patent Blue V and an iodine contrast agent prior to the extra-anatomical video-assisted thoracoscopic surgery (VATS) resection in patients for whom the primary anatomical resection in terms of segmentectomy or lobectomy was not indicated. Methods: The data of consecutive patients with pulmonary nodules located ≤ 30 mm from the parietal pleura, who were indicated for VATS extra-anatomical resection between 2017 to 2023, were retrospectively reviewed and analyzed. All patients indicated for VATS resection underwent color marking of the area with the pulmonary lesion under CT-guided control immediately before the surgery. The primary outcome was the marking success. Morphological lesion characteristics, time from marking to the surgery, procedure related complications, final histology findings and 30day mortality were analyzed. Additionally, we assessed the association of the successful marking and the patient's smoking history. Results: A total of 62 lesions were marked. The successful marking was observed in 56/62 (90.3%) patients. The median time from the lesion marking to the beginning of surgery was 75.0 (IQR 65.0-85.0) minutes. The procedure related pneumothorax was observed in 6 (9.7%) patients, intraparenchymal hematoma in 1 (1.6%) patient. No statistically significant association of the depth of the subpleural lesion's location, occurrence of complications or time from the marking to surgery and the successful marking was observed. The 30day mortality was zero. No association of smoking and successful marking was observed. Conclusions: The method of marking the subpleural pulmonary lesions under CT-guided control with a mixture of Patent Blue V and iodine contrast agent is a safe and effective method with minimal complications. It provides surgeons the precise visualization of the affected pulmonary parenchyma before the planned extra-anatomical VATS resection.

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