Indigo carmine dye for detecting urinary track damage during vaginal surgery.

OBJECTIVE: Unrecognized ureteral and bladder injury increase morbidity and mortality in gynecologic surgery. The primary objective of this study is to analyze the efficiency of a systematic intra-venous (IV) injection of carmine indigo to detect bladder injury in gynecologic vaginal surgery for benign disease. The secondary objective is to analyze the cost and use of carmine indigo. STUDY DESIGN: A retrospective, monocentric study was conducted in a tertiary hospital between January 2018 and October 2021. All patients undergoing a vaginal surgery of hysterectomy for benign disease or anterior prolapse were systematically included. Patients can be systematically included by the automatic coding of surgery. After anesthesia, during the patient's installation, an intravenous injection of 5 mL of intravenous indigo carmine (Carmyne®) diluted in 100 mL of physiological serum was systematically administered by the anesthesia team. Intraoperative cystoscopy was performed only in cases of suspected associated ureteral injury. RESULTS: We recorded 443 vaginal hysterectomies for benign disease and 95 vaginal anterior prolapse surgeries. There were 6 (1,4%) bladder injuries during vaginal hysterectomies and 1 (1,1%) bladder injury during vaginal prolapse surgery. All bladder injuries were diagnosed intraoperatively. No ureteral injury was diagnosed in this series of patients. No complication related to IV indigo carmine injection was found. In this tertiary hospital, 1085 ampoules of carmine indigo were ordered during the same period, approximatively 270 per year. The total cost to the gynecology and obstetrics department was 19,600 euros, or about 4,900 euros per year. Half of the carmine indigo was used in vaginal surgery and half in laparotomy, caesarean section and endometriosis surgery for suspected bladder or ureteral injury.

Localization Technique Using Mixture of Indigo Carmine and Lipiodol of Pulmonary Nodule via Bronchoscopic Navigation.

Background and Objectives: As the number of minimally invasive surgeries, including video-assisted thoracoscopic surgery, increases, small, deeply located lung nodules are difficult to visualize or palpate; therefore, localization is important. We studied the use of a mixture of indigo-carmine and lipiodol, coupled with a transbronchial approach-to achieve accurate localization and minimize patient discomfort and complications. Materials and Methods: A total of 60 patients were enrolled from May 2019 to April 2022, and surgery was performed after the bronchoscopy procedure. Wedge resection or segmentectomy was performed, depending on the location and size of the lesion. Results: In 58/60 (96.7%) patients, the localization of the nodules was successful after localization, and 2/60 required c-arm assistance. None of the patients complained of discomfort during the procedure; in all cases, margins were found to be free from carcinoma, as determined by the final pathology results. Conclusions: We recommend this localization technique using mixture of indigo carmine and lipiodol, in concert with the transbronchial approach, because the procedure time is short, patient's discomfort is low, and success rate is high.

Thermal tissue damage caused by new endoscope model due to light absorption.

BACKGROUND AND AIM: Bright endoscopic light sources improve the visibility of the intestinal mucosa. A newly launched endoscopic system developed by Olympus Corporation (Tokyo, Japan) in 2020 required modification to prevent heat-induced tissue damage, which reportedly occurs during magnifying chromoendoscopy. We investigated the mechanism of this phenomenon by evaluating the rise in temperature of stained and unstained porcine mucosa using the new and previous endoscopic systems. METHODS: Surface temperatures of stained (India ink, 0.05% crystal violet, 0.5% methylene blue, or 0.2% indigo carmine) and unstained porcine mucosa were evaluated using infrared imaging after contact with the new endoscopic system before it was modified (system-EVIS X1; scope-GIF-EZ1500) and compared with a previous endoscopic system (system-EVIS EXERAIII; scope-GIF-H190). We performed histological analysis of the porcine mucosa stained with 0.05% crystal violet after contact with the new endoscope to evaluate the degree of tissue damage. RESULTS: Surface temperatures remained < 40°C when the new endoscope was in contact with the unstained mucosa. However, the maximum surface temperature rose to > 70°C when the new endoscope was in contact with the stained mucosa (stained other than indigo carmine). Histological analysis revealed cavity formation in porcine epithelium stained with crystal violet where the endoscope made contact for ≥ 5 s . Using the previous endoscope, the maximum surface temperature of stained mucosa remained below approximately 60°C, and the surface temperature of the unstained mucosa remained below 30°C. CONCLUSIONS: Heat transfer by light absorption could cause heat-induced tissue damage during magnifying chromoendoscopy using the new endoscope.

Indigo Carmine Hemodynamic Studies to Treat Vasoplegia Induced by Compound 48/80 in a Swine Model of Anaphylaxis.

INTRODUCTION: There are many reasons to believe that the nitric oxide/guanosine 3'5' - cyclic monophosphate (or NO/cGMP) pathway on vasoplegic states is underestimated. To study indigo carmine (IC) as an alternative to methylene blue was the investigation rationale. METHODS: The IC (3mg/kg intravenous infusion) study protocol included five experimental groups; 1) Control group - saline was injected at 0 and 10 minutes; 2) IC group - IC was injected at 0 and saline at 10 minutes; 3) compound 48/80 (C48/80) group - C48/80 was injected at 0 minute and saline at 10 minutes; 4) C48/80 + IC group - C48/80 was injected at 0 minute and IC at 10 minutes; and 5) IC + C48/80 group - IC was injected at 0 minute and C48/80 at 10 minutes. The studies were carried out by registering and measuring hemodynamic and blood gasometric parameters, including continuous cardiac output. RESULTS: 1) The effects of the drugs (IC and C48/80) were more evident in the first 20 minutes of recording; 2) hypotensive responses were more pronounced in the C48/80 groups; 3) IC isolated or applied before C48/80 caused transient pulmonary hypertension; and 4) after the first 20 minutes, the pressure responses showed stability with apparent hypotension more pronounced in the C48/80 groups. Clinical observations showed significant hemodynamic instability and catastrophic anaphylactic reactions (agitation, pulmonary hypertension, severe bronchospasm, urticaria, high-intensity cyanosis, violent gastric hypersecretion, and ascites). CONCLUSION: A global results analysis showed differences between groups only in the first 20 minutes of the experiments.

Efficacy and safety of short-term therapy with indigo naturalis for ulcerative colitis: An investigator-initiated multicenter double-blind clinical trial.

INTRODUCTION: Indigo naturalis (IN) is a blue pigment extracted from Assam indigo and other plants and has been confirmed to be highly effective for ulcerative colitis (UC) treatment in several clinical studies. OBJECTIVE: We conducted a multicenter double-blind study to confirm the efficacy and safety of short-term IN administration. METHODS: A multicenter, randomized controlled trial was conducted between December 2015 and October 2018 in our facilities. Forty-six patients with mild to moderate active UC (Lichtiger index: 5-10) were randomly assigned to the IN group or the placebo group and received 5 capsules (500 mg) twice a day for 2 weeks. We investigated the efficacy according to blood tests and the Lichtiger index before and after administration, and we also examined adverse events. RESULTS: The analysis included 42 patients (20 males, 22 females) with an average age of 45 years. Nineteen patients were assigned to the placebo group, and 23 were assigned to the IN group. After treatment administration, in the placebo group, no change in the Lichtiger index was observed (7.47 to 6.95, p = 0.359), and hemoglobin was significantly reduced (12.7 to 12.4, p = 0.031), while in the IN group, the Lichtiger index (9.04 to 4.48, p = 0.001) and albumin (4.0 to 4.12, p = 0.022) improved significantly. Mild headaches were observed in 5 patients and 1 patient in the IN and placebo groups, respectively. CONCLUSIONS: Short-term administration of IN is highly effective without serious adverse events such as pulmonary hypertension or intussusception and may prevent the occurrence of serious adverse events.

Ischemic colitis induced by indigo naturalis in a patient with ulcerative colitis: a case report.

BACKGROUND: Indigo naturalis is a Chinese herbal medicine that has currently been used to treat various inflammatory diseases, including ulcerative colitis. Recently, there are several reports concerning severe adverse events associated with indigo naturalis. CASE PRESENTATION: We described a case of a 44-year-old female with ulcerative colitis who presented with lower abdominal pain and hematochezia. She stopped taking her medicine for ulcerative colitis and started oral indigo naturalis 3 months before admission. Computed tomography showed segmental edematous wall thickening of the descending and sigmoid colon. Colonoscopy findings revealed erythema, edema, and submucosal hemorrhage, the surface of which presented a dark blue pigmentation. The histologic finding was consistent with ischemic colitis. We therefore considered an ischemic colitis induced by indigo naturalis, and the patient improved after supportive care and withdrawal of indigo naturalis. CONCLUSION: Indigo naturalis has currently been used in the patients with ulcerative colitis as an alternative therapy. However, physicians should be aware of possible severe adverse events such as ischemic colitis.

The Utility of Indigo Carmine and Lipiodol Mixture for Preoperative Pulmonary Nodule Localization before Video-Assisted Thoracic Surgery.

PURPOSE: To evaluate the safety and efficacy of a mixture of indigo carmine and lipiodol (MIL) as a marker of pulmonary nodule before video-assisted thoracic surgery (VATS). MATERIALS AND METHODS: One hundred sixty-eight sessions of pulmonary marking were performed using MIL before VATS for 184 nodules (mean size, 1.2 ± 0.6 cm; range, 0.3-3.6 cm) on 157 patients (83 men and 74 women; median age, 66 years). The mean distance between the lung surface and the nodule was 0.8 ± 0.7 cm (range, 0-3.9 cm). MIL was injected near the nodule using a 23-gauge needle. Mean number of 1.2 ± 0.4 (range, 1-3) punctures were performed in a session for the target nodules, with mean number of 1.1 ± 0.3 (range, 1-3). Successful targeting, localization, and VATS were defined as achievement of lipiodol accumulation at the target site on computed tomography, detection of the nodule in the operative field by fluoroscopy or visualization of dye pigmentation, and complete resection of the target nodule with sufficient margin, respectively. RESULTS: The successful targeting rate was 100%, and the successful localization rate was 99.5%, with dye pigmentation for 160 nodules (87.0%) and intraoperative fluoroscopy for 23 nodules (12.5%). Successful VATS was achieved for 181 nodules (98.4%). Two nodules (1.1%) were not resectable, and surgical margin was positive in 1 nodule (0.5%). Complications requiring interventions occurred in 5 sessions (3.0%) and included pneumothorax with chest tube placement (n = 3) and aspiration (n = 2). No complication related to the injected MIL occurred. CONCLUSIONS: MIL was safe and useful for preoperative pulmonary nodule marking.

Coloración dental por índigo carmín. Excipientes: la asignatura pendiente / Indigo carmine related tooth discolouration. Excipients: a pending subject

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Severe hypertension and tachycardia during transforaminal endoscopic discectomy - Is indigocarmine to blame?

Endoscopic transforaminal discectomy is a minimally invasive technique used for the surgical treatment of herniated discs. Indigocarmine is a dye which is widely used to identify the ureteral orifice in urologic procedures. Hemodynamic effects such as hypotension and anaphylaxis in addition to hypertension, bradycardia and atrioventricular block have been reported in intravenous application of indigocarmine. The aim of this case report is to prepare anesthesiologists for such cases and make them consider invasive blood pressure monitorization. Both patients had radicular pain radiating to the leg and scheduled to undergo transforaminal endoscopic discectomy. Intraoperative vital signs were within normal limits, however severe hypertension and tachyarrhythmia developed following the injection. Hemodynamics in both patients returned to normal following lidocaine and nitroglycerine injection.

Effect of virtual-assisted lung mapping in acquisition of surgical margins in sublobar lung resection.

OBJECTIVE: Virtual-assisted lung mapping is a preoperative bronchoscopic multi-spot dye-marking technique. This study aimed to examine the efficacy of virtual-assisted lung mapping for obtaining sufficient surgical margins in sublobar lung resection. METHODS: The multicenter, prospective, single-arm study was conducted from September 2016 to July 2017 in 19 registered centers. Patients who required sublobar lung resection and careful determination of resection margins underwent virtual-assisted lung mapping followed by thoracoscopic surgery. Successful resection was defined as resection of the lesion with margins greater than the lesion diameter or 2 cm using the preoperatively planned resection without additional resection. We defined the primary goal of the study as achieving successful resection in 95% of lesions. RESULTS: The resection of 203 lesions (average diameter, 9.6 ± 5.3 mm) was intended in 153 patients. The lesions included pure and mixed ground-glass nodules (75 [35.9%] and 36 [17.2%], respectively), solid nodules (91 [43.5%]), and others (7 [3.3%]). Surgical procedures included wedge resection (131, 71.2%), segmentectomy (51, 27.7%), and others (2, 1.1%). Successful resection was achieved in 178 lesions (87.8% [95% confidence interval, 82.4-91.9%]), and virtual-assisted lung mapping markings successfully aided in the identification of 190 lesions (93.6% [95% confidence interval, 89.3-96.5%]). Multivariable analysis showed that the most significant factor affecting resection success was the depth of the necessary resection margin (P = .0072). CONCLUSIONS: This study showed that virtual-assisted lung mapping has reasonable efficacy, although the successful resection rate did not reach the primary goal. The depth of the required margin was the most significant factor leading to resection failure.

Efficacy of Indigo Naturalis in a Multicenter Randomized Controlled Trial of Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Indigo naturalis (IN) is a traditional Chinese medicine that contains ligands for the aryl hydrocarbon receptor and promotes regeneration of the mucosa by inducing production of interleukin 22. IN might induce mucosal healing in patients with ulcerative colitis (UC). We performed a randomized controlled trial to investigate the safety and efficacy of IN in patients with UC. METHODS: We performed a multicenter, double-blind trial evaluating the safety of 86 patients in Japan with active UC (Mayo scores of 6 or more), enrolled from March 30 through December 27, 2016. Patients were randomly assigned to groups and given a daily dose of 0.5, 1.0, or 2.0 g IN or placebo (1:1:1:1 ratio) for 8 weeks. The primary endpoint was the rate of clinical response at week 8, defined as a 3-point decrease in the Mayo score and a decrease of at least 30% from baseline, with a decrease of at least 1 point for the rectal bleeding subscore or absolute rectal bleeding score of 0-1. The main secondary endpoint was the rate of clinical remission at week 8, defined as a Mayo score or ≤2 and no subscores with a value >1. Mucosal healing was also assessed at week 8. RESULTS: The trial was terminated because of an external reason: a report of pulmonary arterial hypertension in a patient who used self-purchased IN for 6 months. In the intent-to-treat analysis, we observed a significant, dose-dependent linear trend in proportions of patients with clinical responses (13.6% with a clinical response to placebo; 69.6% to 0.5 g IN; 75.0% to 1.0 g IN; and 81.0% to 2.0 g IN) (Cochran-Armitage trend test P < .0001 compared with placebo). Proportions of patients in clinical remission at week 8 were significantly higher in the 1.0 g IN group (55.0%, P = .0004) and the 2.0 g IN group (38.1%, (P = .0093) than in the placebo group (4.5%). Proportions of patients with mucosal healing were 13.6% in the placebo group, 56.5% in the 0.5 g IN group, 60.0% in the 1.0 g IN group, and 47.6% in the 2.0 g IN group (P = .0278 compared with placebo). Although mild liver dysfunction was observed in 10 patients who received IN, no serious adverse events were observed. CONCLUSIONS: In a randomized, placebo-controlled trial, we found 8 weeks of IN (0.5-2.0 g per day) to be effective in inducing a clinical response in patients with UC. However, IN should not yet be used because of the potential for adverse effects, including pulmonary arterial hypertension. Clinical Trials Registry no: UMIN000021439 (http://www.umin.ac.jp/ctr/).

Effects of indigo carmine intravenous injection on oxygen reserve index (ORi™) measurement.

To retrospectively investigate the effects of indigo carmine intravenous injection on oxygen reserve index (ORi™) in 20 patients who underwent elective gynecologic surgery under general anesthesia. The study subjects were patients who underwent elective gynecologic surgery under general anesthesia between April 2016 and January 2017, and were administered a 5-ml intravenous injection of 0.4% indigo carmine for clinical purposes during surgery with ORi monitoring. Changes in ORi within 20 min after indigo carmine injection were observed. A relevant decrease in ORi was defined as ≥ 10% reduction in ORi from pre-injection level. ORi rapidly decreased after indigo carmine intravenous injection in all patients. In 10 of 19 patients, ORi decreased to 0 after indigo carmine injection. The median lowest value of ORi was 0 (range 0-0.16) and the median time to reach the lowest value of ORi was 2 min (range 1-4 min) after injection. ORi values returned to pre-injection levels within 20 min in 13 of 19 patients, and the median time to return to pre-injection levels was 10 min (range 6-16 min) after injection. During ORi monitoring it is necessary to consider the rapid reduction in ORi after intravenous injection of indigo carmine.

Indigo Naturalis Ameliorates Oxazolone-Induced Dermatitis but Aggravates Colitis by Changing the Composition of Gut Microflora.

BACKGROUND: Indigo naturalis (IND) is an herbal medicine that has been used as an anti-inflammatory agent to treat diseases including dermatitis and inflammatory bowel disease in China. However, the mechanism by which IND exerts its immunomodulatory effect is not well understood. METHODS: A murine model of dermatitis and inflammatory bowel disease, both induced by oxazolone (OXA), was treated with IND. The severity of dermatitis was evaluated based on ear thickness measurements and histological scoring. The severity of colitis was evaluated by measuring body weight, histological scoring, and endoscopic scoring. The expression of inflammatory cytokines in ear and colon tissue was evaluated using real-time PCR. 16S rRNA DNA sequencing of feces from OXA-induced colitis mice was performed before and after IND treatment. The effects of IND on OXA-induced colitis were also evaluated after depleting the gut flora with antibiotics to test whether alteration of the gut flora by IND influenced the course of intestinal inflammation in this model. RESULTS: IND treatment ameliorated OXA dermatitis with a reduction in IL-4 and eosinophil recruitment. However, OXA colitis was significantly aggravated in spite of a reduction in intestinal IL-13, a pivotal cytokine in the induction of the colitis. It was found that IND dramatically altered the gut flora and IND no longer exacerbated colitis when colitis was induced after gut flora depletion. CONCLUSIONS: Our data suggest that IND could modify the inflammatory immune response in multiple ways, either directly (i.e., modification of the allergic immune cell activity) or indirectly (i.e., alteration of commensal compositions).