ABSTRACT
COVID-19 is a global catastrophic event that causes severe acute respiratory syndrome. The mechanism of the disease remains unclear, and hypoxia is one of the main complications. There is no currently approved protocol for treatment. The microbial threat as induced by COVID-19 causes the activation of macrophages to produce a huge amount of inflammatory molecules and nitric oxide (NO). Activation of macrophages population into a proinflammatory phenotype induces a self-reinforcing cycle. Oxidative stress and NO contribute to this cycle, establishing a cascade inflammatory state that can kill the patient. Interrupting this vicious cycle by a simple remedy may save critical patients’ lives. Nitrite, nitrate (the metabolites of NO), methemoglobin, and prooxidant-antioxidant-balance levels were measured in 25 ICU COVID-19 patients and 25 healthy individuals. As the last therapeutic option, five patients were administered methylene blue-vitamin C–N-acetyl Cysteine (MCN). Nitrite, nitrate, methemoglobin, and oxidative stress were significantly increased in patients in comparison to healthy individuals. Four of the five patients responded well to treatment. In conclusion, NO, methemoglobin and oxidative stress may play a central role in the pathogenesis of critical COVID-19 disease. MCN treatment seems to increase the survival rate of these patients. Considering the vicious cycle of macrophage activation leading to deadly NO, oxidative stress, and cytokine cascade syndrome; the therapeutic effect of MCN seems to be reasonable. Accordingly, a wider clinical trial has been designed. It should be noted that the protocol is using the low-cost drugs which the FDA approved for other diseases.
ABSTRACT
In this paper, we raise the hypothesis that Methylene Blue may be a treatment option for Corona Virus Disease of 2019 specially when combined with Non Steroid Anti-Inflammatory Drugs. In previous publications including ours, the role of kininogen system has been postulated. A correlation between clinical findings of the disease and this mechanism has been drawn to denote a pivotal role of kininogen-kallikrein system in pathophysiology of the disease. Therein the possible role of Icatibant, Ecallantide and Aprotinin in the treatment of this disease has been raised. Here we want to emphasize on an important post-receptor mechanism of bradykinin that is Nitric Oxide. We came to this aim because we found out how access to these novel treatment nominees may be expensive and unaffordable. For this reason we are focusing on possible role of an old albeit “mysterious” drug namely Methylene Blue. This medication may abort effects of Bradykinin by inhibition of Nitric Oxide synthase inhibitor and promote oxygen saturation while it is inexpensive and ubiquitously accessible. Clinical studies cannot be over emphasized.
ABSTRACT
SARS-CoV-2 infection generally begins in the respiratory tract where it can cause bilateral pneumonia. The disease can evolve into acute respiratory distress syndrome and multi-organ failure, due to viral spread in the blood and an excessive inflammatory reaction including cytokine storm. Antiviral and anti-cytokine drugs have proven to be poorly or in-effective in stopping disease progression, and mortality or serious chronic damage is common in severely ill cases. The low efficacy of antiviral drugs is probably due to late administration, when the virus has triggered the inflammatory reaction and is no longer the main protagonist. The relatively poor efficacy of anti-cytokine drugs is explained by the fact that they act on one or a few of the dozens of cytokines involved, and because other mediators of inflammation – reactive oxygen and nitrogen species – are not targeted. When produced in excess, reactive species cause extensive cell and tissue damage. The only drug known to inhibit the excessive production of reactive species and cytokines is methylene blue, a low-cost dye with antiseptic properties used effectively to treat malaria, urinary tract infections, septic shock, and methaemoglobinaemia. We propose testing methylene blue to contrast Covid-related acute respiratory distress syndrome, but particularly suggest testing it early in Covid infections to prevent the hyper-inflammatory reaction responsible for the serious complications of the disease.
ABSTRACT
The Covid-19 epidemic transformed life in our cities and continues to cause numbers of deaths. Although it often occurs in mild form, cases that develop acute respiratory distress syndrome (ARDS), cardiovascular damage, shock, or multi-organ dysfunction are frequent and indicate a systemic inflammatory response
The Covid-19 epidemic transformed life in our cities and continues to cause numbers of deaths. Although it often occurs in mild form, cases that develop acute respiratory distress syndrome (ARDS), cardiovascular damage, shock, or multi-organ dysfunction are frequent and indicate a systemic inflammatory response [1]. The inflammatory response is triggered by activation of monocytes and alveolar macrophages, which produce, and release into the extracellular compartment, bioactive mediators including reactive oxygen species (ROS), reactive nitrogen species (RNS), and cytokines. When the production of these mediators exceeds the capacity of tissues to neutralize them, oxidative stress occurs, and is a major contributor to alveolar cell death and endothelial injury. Damage to the vascular endothelium can lead to multi-organ dysfunction [2]. This inflammatory response is common to many diseases, including septic shock [3]. Drugs that combat the cytokine storm (anakinra, tocilizumab) have been proposed for the treatment of Covid-19-related ARDS [4], but other therapeutic strategies need to be explored. Data from animal studies indicate that ROS and RNS play fundamental roles in the pathogenesis of ARDS [5], and high levels of RNS are involved in the multi-organ failure of septic shock [6]. Nevertheless, drugs that minimize the harmful effects of these species have not been introduced into clinical practice. Methylene blue, an old anti-malarial drug currently used to treat methemoglobinemia, has been used successfully to treat septic shock [7] with minimal adverse effects. It acts effectively as an antioxidant on RNS by lowering the bio-availability of nitric oxide [8], which is the progenitor of strongly oxidative nitrogenbased molecules. Methylene blue also prevents ROS production by inhibiting the action of xanthine oxidase [9]. Based on these data methylene blue appears worth trying to contrast Covid-19-related pneumonia when the first symptoms of ARDS appear. As regards dose, methylene blue was administered at 1–2 mg/kg in a single bolus or lower dose infusion in septic shock patients; methylene blue has a dose-dependent effect on pulmonary vascular resistance, and venous infusion of doses above 2 mg / kg should be prudently avoided [10]. Continuous infusion would allow for titration based on response and result in a lower dose overall. We therefore suggest that, similarly to what was experienced in septic shock [11], a bolus of 1 mg/kg, followed after 2 h by infusion of 0.5 mg/kg/h for four hours would be an appropriate starting point. The earlier the start of treatment, the better the expected result, and taking low-dose methylene blue (120–180 mg/day orally for ten or fifteen days) from the first Covid-19 symptoms could prevent the onset of ARDS and avoid the need for hospitalization
Summary
Ifosfamide is an alkylating agent used in the treatment of a variety of solid tumours. Ten to 15% of patients treated with ifosfamide develop an encephalopathy. Methylene blue (MB) may be used in the treatment of this encephalopathy. The purpose of this study was to evaluate the neuroprotective effect of MB in these patients and to review the literature. Between 1993 and 1997, 52 patients (age 16–77 years) with solid tumours were treated with ifosfamide in dosages ranging from 3 to 5 g m–2 q3w when given in combination schedules and up to 12 g m–2 q4w when given as a single agent. Twelve patients developed central nervous system (CNS) depression, defined as National Cancer Institute Common Toxicity Criteria (NCI-CTC) neurocortical toxicity grade 2 or higher. Eight were treated with MB at a dose of 6 ´ 50 mg day–1 intravenously (i.v.). Four recovered fully within 24 h, two recovered partially after 24 h and completely after 48 h while two recovered only after 72 h. Four patients did not receive MB and all recovered only after 48 h. Three patients received prophylaxis with MB at a dose of 4 ´ 50 mg day–1 i.v. for the subsequent chemotherapy cycles. Two developed milder encephalopathy; one had no CNS depression at all. We conclude that MB is an effective treatment for ifosfamide-induced encephalopathy. Our findings suggest that it may also be used as a prophylactic agent.
Abstract. Purpose
The aim of this prospective study was to analyze the safety of methylene blue dye (MBD) and compare its efficacy with that of isotopic mapping for sentinel lymph node (SLN) identification in breast cancer.
Patients and Methods: The SLN procedure, involving isotopic mapping and MBD (subareolar intraparenchymal injections of 2 mL, 10 mg/mL), was performed on 100 patients with early breast cancer.
Results: The procedure was safe with a success rate of 99% ; SLNs were, respectively, found in 65% by MBD, in 73% by lymphoscintigraphy and in 94% by gamma-probe. Out of 40 metastatic SLNs, 37 were “hot” and 32 stained. Digital examination allowed the detection of 2 additional metastatic LNs. Conclusion: MBD is safe and combination mapping associated with digital examination is the superior method. Modification of the procedure, favouring injections of dilute MBD (4 mL, 1.25 mg/mL) increases MBD efficiency (90% ) and maintains low rates of complications
Abstract
Background : Methylene blue dye is easy to obtain in developing countries and can be used in sentinel lymph node mapping for breast cancer. However, the accuracy of methylene blue alone for sentinel lymph node mapping in breast cancer has not been well defined. In this study, we collected data to assess the feasibility and accuracy of sentinel lymph node biopsy mapped with methylene blue alone in patients with breast cancer.
Methods : We searched the PubMed, EMBASE, and Cochrane Library databases from January 1, 1993, to March 31, 2018. Selected studies had to have a defined group of patients with breast cancer in which MBD alone was used as the mapping technique for SNB.
Results : 18 studies were included in this study. The combined identification rate was 91% [95% confidence interval (CI): 88%-94%, I2 = 68.3%], and the false negative rate was 13% (95% CI: 9%-18%, I2 = 36.7%). The pooled sensitivity, negative predictive value, and accuracy rate were 87% (95% CI: 82%-91%, I2 = 37.5%), 91% (95% CI: 87%-93%, I2 = 32.4%) and 94% (95% CI: 92%-96%, I2 = 29%), respectively.
Conclusions : This meta-analysis found that mapping sentinel lymph node locations with methylene blue dye alone results in an acceptable identification rate but an excessive false negative rate according to the American Society of Breast Surgeons' recommendations. Caution is warranted when using methylene blue dye alone as the mapping method for sentinel lymph node biopsy.
Abstract Breast cancer is the leading malignancy and the second leading cause of cancer-related deaths. Axillary lymph node status is a very important prognostic factor in breast cancer patients; nodal evaluation is therefore a critical part of breast cancer management. Axillary lymph node dissection results in significant morbidity. Sentinel lymph node biopsy (SLNB) is being used in many centers to stage the axilla in planning axillary dissection management of patients and hence plays an important part in reducing morbidity among patients with carcinoma breast. The objectives of this paper is to study the (1) efficacy of sentinel lymph node biopsy in detecting axillary metastasis, (2) location of sentinel lymph node in the axilla, (3) rate of involvement of sentinel lymph nodes, and (4) incidence of skip metastasis. Thirty-five patients with breast cancer with clinically node-negative axilla were selected for the study. Methylene blue dye was injected intralesional and perilesional 20 min prior to surgery. All patients underwent modified radical mastectomy with sentinel lymph node biopsy and axillary dissection and after pathological examination diagnostic statics, namely sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were computed. Sentinel lymph node was identified in all of these patients. Sixty percent patients had pathologically positive lymph nodes in the axilla. 90.48% patients of these had sentinel lymph nodes positive for malignant cells. Incidence of skip metastasis is 9.52%. 88.57% patients had sentinel lymph node mapped to level I lymph nodes. Sensitivity of SLNB is 90.48%, specificity is 85.71%, PPVof is 90.48%, NPV is 85.71%, and accuracy is 88.57%. Sentinel lymph node biopsy is an effective method of staging the axilla and deciding on axillary clearance in patients of carcinoma breast. Unnecessary axillary dissection and associated complications can be prevented in most of patients due to sentinel lymph node biopsy.
Abstract
Background Axillary lymph node dissection is an established procedure in breast cancer staging. However, it is associated with unpleasant side effects. A promising alternative to assess axillary lymph node status in early breast cancer patients is Sentinel Lymph Node Biopsy (SLNB). Isosulfan blue has traditionally been the dye used to identify the Sentinel Lymph Node (SLN). This article is a validation study of SLNB using methylene blue dye and radioactive sulphur colloid in early breast cancer Indian patients. Materials & Methods With written informed consent, 100 patients with cytology or biospy proven carcinoma breast, clinical stage T1/ T2 N0 M0, underwent SLNB using combination of methylene blue dye & radioactive technetium 99m sulphur colloid as a part of validation study from June 2003 to February 2006. After validation study, from March 2006 to February 2007, 35 patients have undergone SLNB followed by complete axillary clearance in only those patients with SLNB being positive for metastases.
Results : Results In all 100 patients of the validation study SLN was identifi ed. Total number of cases with positive axillary nodes was 27, out of which SLN was only positive node for metastases in 69% of cases. The overall sensitivity, specifi city, positive predictive valve and negative predictive valve of SLNB 96.2%, 100%, 100% and 98.6% respectively with false negative rate of 3.7%. In subsequent 35 patients who underwent SLNB followed by complete axillary clearance, SLNs was identifi ed in all the cases.
Conclusions : SLNB is effective in early breast cancer patients of Indian population. SLNB using combination of methylene blue dye and radio-active Tc99m sulphur colloid can stage the axilla with high accuracy & low risk of false negativity in early breast cancer patients
Abstract
Oral cancer is one of the most common neoplasm’s and is ranked eighth in the cancer incidence worldwide. Early detection is of critical importance because survival rates markedly improve. In vivo staining is a simple, inexpensive, and fairly sensitive method. Involved 120 patients (50 with Premalignant Lesion, 50 with OSCC and 20 controls) stained by Methylene Blue (MB). The results of MB uptake were compared with a simultaneous biopsy of these lesions. Pathologically confirmed precancers and cancers were the positive targets of this screening, while hyperkeratosis without dysplasia and no evidence of malignancy were sorted as negative subjects of screening. The results revealed sensitivity of 91.4%, specificity of 66.6%, positive predictive value 97.7% and negative predictive value 33% leading to diagnostic accuracy of MB stain to 90%. We state that MB staining is useful diagnostic tool in community oral cancer screening programmes for high-risk individuals.
Abstract
Sentinel lymph node biopsy (SLNB) has become an accepted standard of care to stage the axilla for clinically node‐negative early stage breast cancer. In experienced hands, studies have shown an acceptable rate of identification of the sentinel lymph node (SLN) with blue dye only. Lymphazurin is occasionally associated with severe allergic reaction, including anaphylaxis and death. The use of methylene blue alone as a method of identifying the SLN in breast cancer has been reported once previously in the literature. Methylene blue may be an acceptable alternative with fewer deleterious side effects. Medical records of patients, who underwent sentinel node mapping between September 2003 and March 2005 by two surgeons at an academic medical center were reviewed. SLN mapping was performed by periareolar injection of 5 cc of 1% methylene blue. All patients with positive SLNs underwent completion axillary node dissection. During the study period, 141 consecutive patients with clinically node‐negative axillas and without evidence of inflammatory breast cancer underwent SLNB with injection of methylene blue only. A SLN was identified in 136 of 141 patients (96.5%). Thirty‐three of 136 SLNs (24%) harbored metastatic disease. No cases of anaphylaxis were noted. In experienced hands, methylene blue alone is a highly sensitive method of detecting SLNs. Avoiding the greater frequency of allergic reactions seen with lymphazurin is an important advantage of methylene blue.
Abstract
Isosulfan blue has been traditionally used as a tracer to map the lymphatic system during identification of the sentinel lymph node. However, allergic reactions may be life threatening. We compared the efficacy of methylene blue dye as a tracer for sentinel lymph node biopsy to isosulfan blue dye. In an analysis of 164 cases, there was no clinical or statistically significant difference in the success rate of sentinel node biopsy (P = 0.22), the number of blue sentinel nodes harvested (P = 0.46), the concordance with radioactive sentinel nodes (P = 0.92), or the incidence of metastases (P = 0.87) when methylene blue tracer was compared to isosulfan blue. No adverse reaction to either blue dye was observed. In conclusion, intraparenchymal injection of methylene blue dye is a reliable tracer for the lymphatic system and nodal identification during sentinel node mapping for breast cancer. It is safe, inexpensive, and readily available.
Abstract
Background : Breast cancer is the main cause of mortality among women. The disease presents high recurrence mainly due to incomplete efficacy of primary treatment in killing all cancer cells. Photodynamic therapy (PDT), an approach that causes tissue destruction by visible light in the presence of a photosensitizer (Ps) and oxygen, appears as a promising alternative therapy that could be used adjunct to chemotherapy and surgery for curing cancer. However, the efficacy of PDT to treat breast tumours as well as the molecular mechanisms that lead to cell death remain unclear.
Methods : In this study, we assessed the cell-killing potential of PDT using methylene blue (MB-PDT) in three breast epithelial cell lines that represent non-malignant conditions and different molecular subtypes of breast tumours. Cells were incubated in the absence or presence of MB and irradiated or not at 640 nm with 4.5 J/cm2. We used a combination of imaging and biochemistry approaches to assess the involvement of classical autophagic and apoptotic pathways in mediating the cell-deletion induced by MB-PDT. The role of these pathways was investigated using specific inhibitors, activators and gene silencing.
Results : We observed that MB-PDT differentially induces massive cell death of tumour cells. Non-malignant cells were significantly more resistant to the therapy compared to malignant cells. Morphological and biochemical analysis of dying cells pointed to alternative mechanisms rather than classical apoptosis. MB-PDT-induced autophagy modulated cell viability depending on the cell model used. However, impairment of one of these pathways did not prevent the fatal destination of MB-PDT treated cells. Additionally, when using a physiological 3D culture model that recapitulates relevant features of normal and tumorous breast tissue morphology, we found that MB-PDT differential action in killing tumour cells was even higher than what was detected in 2D cultures.
Conclusions : Finally, our observations underscore the potential of MB-PDT as a highly efficient strategy which could use as a powerful adjunct therapy to surgery of breast tumours, and possibly other types of tumours, to safely increase the eradication
Abstract
Chromoendoscopy pertains to image-enhanced endoscopic techniques such as dye-based chromoendoscopy with topical dyes such as methylene blue or indigo carmine and electronic chromoendoscopy using narrow-band imaging, flexible spectral imaging color enhancement, and i-scan. Dye-based chromoendoscopy has been demonstrated to improve colorectal dysplasia detection in high-risk patients with long-term inflammatory bowel disease, and electronic chromoendoscopy techniques have been shown to improve characterization of diminutive colorectal lesions, allowing for optical diagnosis during a colonoscopy examination. This article reviews endoscopic imaging using chromoendoscopy techniques for colorectal dysplasia evaluation.
Background and Aim : Endocytoscopy (EC) at ultra-high magnification enables in vivo visualization of cellular atypia of gastrointestinal mucosae. Clear images are essential for precise diagnosis by EC. The aim of the present study was to evaluate the optimal staining method for EC in the colon.
Methods : Thirty prospectively enrolled patientswere allocated 1:1:1 to three distinct staining methods: 0.05% crystal violet (CV) alone, 1% methylene blue (MB) alone, or CV + MB (CM double). Normal rectal mucosae were stained with each dye and videos of EC images were recorded. Visibility of nuclei and gland formation after staining were evaluated as ‘recognizable’ or ‘not recognizable’. Time for each parameter to become ‘recognizable’ was measured, and the average times for the three staining regimens were compared.
Results : MB alone and CM double staining resulted in ‘recognizable’ (102 } 27 vs 89 } 22 s, P = 0.263) nuclei within comparable periods of time, whereas CV alone was unable to identify nuclei. Gland formation became ‘recognizable’ sooner after CM double staining than after MB alone (61 } 16 vs 108 } 24 s, P < 0.001).
Conclusions : Double staining with CV and MB, which rapidly provided recognizable images of both nuclei and gland formation, is an appropriate staining regimen for colonic EC.
Abstract
In the United States, colorectal cancer (CRC) is the second-leading cause of cancer-related deaths. The most effective strategy for prevention of CRC is to screen for and remove precancerous polyps. There are various ways to screen for CRC. In the United States, the most common method is colonoscopy. Polyps are classified primarily through pathology. Size is the primary risk factor for malignancy. In general, the bigger the polyp, the greater the risk for malignancy. There are 3 basic options for removal: standard polypectomy; advanced resection techniques, known as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD); and surgical removal. In the past 10 years, the use of surgical removal has significantly decreased. Noninvasive, nonmalignant polyps can be removed endoscopically. EMR and ESD are very effective and achieve similar clinical outcomes. Both procedures begin with a submucosal injection. The submucosal lift is one of the most significant advances that have been made in polypectomy. Traditionally, the approach to achieving a submucosal lift has relied on the use of a saline solution. Saline is inexpensive and widely available, but it dissipates quickly. Various viscous agents have been added to saline to maintain mucosal lifting throughout the procedure. Although most are effective, they are used off-label. Newer methods for the submucosal lift procedure use a combination of a blue dye, such as methylene blue or indigo carmine, and a viscous agent to maintain the vertical elevation. The major advantage of using a blue dye is that it clearly distinguishes what has been lifted from what has not been lifted. Other advances in polypectomy techniques include the use of cold snare polypectomy and high-definition colonoscopes. The quality of the colonoscopy can also be improved if a physician knows and monitors his or her adenoma detection rate.
Precise surgical debridement of wounds is to achieve wound closure. The authors describe their experience with a technique using topical methylene blue to facilitate precise surgical debridement. In this technique, methylene blue dye is applied topically to the wound surface at the onset of surgery. The stained wound site is then wiped to remove dye from the surface of normal epithelium; eschar, nonviable tissue, and granulation tissue remain stained. The methylene blue-stained tissue is surgically removed, and the newly debrided surface of the wound is assessed for adequate vascularity and biopsied to verify presence of bacteriologic balance before closure. The authors have used this technique in more than 200 wound debridements during the past year, including acute surgical or traumatic wounds, acute and subacute burn wounds, chronic granulating wounds, partially epithelialized wounds, sinus tracts, and fistulae. No adverse reactions have been noted, even on patients undergoing multiple applications through serial operations. Topical application of methylene blue to wounds with mixed tissue content helps to distinguish between viable and nonviable tissue and between epithelialized and nonepithelialized areas, facilitating more precise and complete wound debridement.
Background : The discovery of nitric oxide as mediator in cardiac postoperative vasoplegia encourages the use of inhibitory drugs such as methylene blue. This drug has been used with favorable results in isolated cases. The purpose of this article is to analyze the incidence of the postoperative vasoplegic syndrome, to consider its prognosis, and to evaluate the effect of intravenous methylene blue on mortality.
Methods : Cardiac surgery patients were consecutively included. Vasoplegic syndrome was defined by the presence of the following five criteria: (1) hypotension, (2) low filling pressures, (3) high or normal cardiac index, (4) low peripheral resistance, and (5) vasopressor requirements. Those with vasoplegia were randomized to receive 1.5 mg/Kg of methylene blue or a placebo. A p value less than 0.05 was considered significant. Results. Six hundred thirty eight cardiac surgery patients were consecutively included in this study. Fifty-six of these patients fulfilled vasoplegia criteria (8.8%) resulting in higher mortality (10.7% or 6 of 56 patients vs 3.6% or 21 of 582 patients; p value _ 0.02). Those treated with methylene blue showed morbidity and mortality reductions (0% versus 21.4% or 6 of 28 patients; p value _ 0.01). The duration of the vasoplegic syndrome was shorter in those patients treated with the drug, lasting less than 6 hours in all patients. Patients in the control group showed a slower recovery, lasting more than 48 hours in 8 patients (p value _ 0.0007).
Conclusions : . Vasoplegic postoperative syndrome was seen in 8.8% of all patients. Outcome in patients with vasoplegia was worse with increased morbidity and mortality. The use of methylene blue reduced the high mortality in this population.
Background : . Angiotensin-converting enzyme inhibitors, calcium channel blockers, and preoperative intravenous heparin use are independent risk factors for vasoplegic syndrome after cardiac surgery. We prospectively studied whether preoperative methylene blue administration would prevent the vasoplegic syndrome in these high-risk patients.
Methods : . One hundred patients scheduled for coronary artery bypass graft surgery who were at high risk for vasoplegia because they were preoperatively using angiotensin- converting enzyme inhibitors, calcium channel blockers, and heparin were randomly assigned to either receive preoperative methylene blue (group 1, n _ 50) or not receive it (group 2, controls, n _ 50). Methylene blue (1% solution) was administered intravenously at a dose of 2 mg/kg for more than 30 minutes, beginning in the intensive care unit 1 hour before surgery.
Results : Although similar in terms of all demographic and operative variables, the two groups differed significantly in terms of vasoplegic syndrome incidence (0% in group 1[0 of 50] vs 26% in group 2 [13 of 50]; p < 0.001). In 6 patients, the vasoplegic syndrome was refractory to norepinephrine. Four of these patients survived; the other 2 had vasoplegic syndromes that were refractory to aggressive vasopressor therapy, and they ultimately died of multiorgan failure. Stroke occurred in 1 patient. The two study groups also differed significantly in terms of average intensive care unit stay (1.2 _ 0.5 days in group 1 vs 2.1 _ 1.2 days in group 2; p < 0.001) and average hospital stay (6.1 _ 1.7 days in group 1 vs 8.4 _ 2.0 days in group 2; p < 0.001).
Conclusions : Our results suggest that preoperative methylene blue administration reduces the incidence and severity of vasoplegic syndrome in high-risk patients, thus ensuring adequate systemic vascular resistance in both operative and postoperative periods and shortening both intensive care unit and hospital stays.
ABSTRACT
Objective : To conduct a systematic review of the literature on vesicovaginal fistula (VVF), including reporting on the aetiology, in both developed and underdeveloped countries; diagnosis; intraoperative prevention; and management.
Methods : We conducted a systematic review of the literature on VVF through the PubMed and the Cochrane Library according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search was conducted from 1985 to 2018 in English, using the keywords ‘fistula’ and ‘vesicovaginal fistula’. Prospective studies were preferred; however, retrospective studies and case reports were used when no prospective studies were available. All authors’ extracted relevant data related to the proposed review of VVF and carefully examined collected articles.
Results : In all, 116 relevant articles were identified and 43 articles were included in this systematic review. The outcome of surgical reconstruction was >90%, but the outcome may be suboptimal in radiotherapy (RT)-induced VVFs. Absolute indications for an abdominal approach included: ureteric involvement, the need for concomitant bladder augmentation, severe vaginal stenosis, and an inability to tolerate the dorsal lithotomy position (e.g. due to muscular spasticity). Typically, it was recommended to wait at least 3 months to allow the inflammatory response to subside before definitive surgery. Early fistula repair can be performed in the absence of infection and in patients who have not received pelvic RT.
Conclusion : VVF is rare in developed countries. Surgical treatment is the primary method of repair. The outcome of surgical reconstruction exceeds 90%, but the outcome may be suboptimal in RT-induced VVFs.
Abstract Vesicovaginal fistula (VVF) is still a major cause for concern in many developing countries. It represents a significant morbidity in female urology. Continual wetness, odor, and discomfort cause serious social problems. The diagnosis of the condition has traditionally been based on clinical methods and dye testing with Methylene Blue. A successful repair of such fistulas requires an accurate diagnostic evaluation and timely repair using procedures that exploit basic surgical principles and the application of interposition flaps. The method of closure depends on the surgeon’s training and experience. The main complication of VVF surgery is recurrent fistula formation.
Rectovaginal fistulas are abnormal epithelial-lined connections between the rectum and vagina. They can be quite bothersome to both the patient and the surgeon due to their irritating and embarrassing symptoms and high failure rate after repair. An individualized, systematic approach to these fistulas based on their size, location, and etiology provides a more concise treatment plan. Supplemental studies may be necessary to confirm the presence of a fistula or to determine the extent of underlying disease. Endorectal and transvaginal ultrasounds may be used to identify a low fistula tract. Alternatively, a vaginal tampon can be inserted followed by instillation of a methylene blue enema. Treatment options of medical therapy, advancement flaps, plugs, fistula ligation, and tissue interposition are discussed.
Abstract Objective : We previously demonstrated that upregulation of renal inducible nitric oxide synthase (iNOS) is associated with proximal tubule injury during systemic inflammation in humans. In this study we investigated the short-term effect of methylene blue (MB), an inhibitor of the NO pathway, on kidney damage and function in septic shock patients. Design and setting: A prospective clinical study conducted in an intensive care unit. Patients: Nine patients (four men, five women, mean age 71 } 3 years) with confirmed or suspected bacterial infection and with refractory septic shock defined as a mean arterial pressure ≤ 70 mmHg despite norepinephrine infusion ≥ 0.2 μg/kg per minute. Interventions: A 4 h continuous intravenous infusion of 1 mg/kg MB per hour. Measurements and results: The urinary excretion of NO metabolites decreased with median 90% (range 75–95%) from baseline to 6 h after MB administration. The first 24 h creatinine clearance improved by 51% (18–173%) after MB treatment but was still strongly impaired. During the first 6 h after the start of MB treatment both the urinary excretion of cytosolic glutathione S-transferase A1-1 and P1-1, markers for proximal and distal tubule damage, respectively, decreased by 45% (10–70%) and 70% (40–85) vs. baseline. After termination of the MB infusion the NO metabolites and markers of tubular injury returned to pretreatment levels.
Conclusions : In septic patients with refractory shock short-term infusion of MB is associated with a decrease in NO production and an attenuation of the urinary excretion of renal tubular injury markers.
Abstract
Background : : Plasma nitric oxide (NO) levels have been found to be high in haemodialysis (HD) patients, especially in those prone to hypotension in dialysis. The aim of the study was to prevent dialysis hypotension episodes by i.v. administration of methylene blue (MB), an inhibitor of NO activity and/or production.
Methods : MB was given i.v. in 18 stable HD patients with hypotensive episodes during almost every dialysis, in 18 HD patients without hypotension during dialyses, and in five healthy controls. MB was given as a bolus of 1 mg/kg bodyweight followed by a constant infusion of 0.1 mg/kg bodyweight lasting 210 min until the end of the dialysis session and only as a bolus on a non-dialysis day. Systolic and diastolic blood pressures (BP) were measured at 10-min intervals during HD sessions with or without MB and on a non-dialysis day with MB
Results : In hypotension-prone patients, MB completely prevented the hypotension during dialysis and increased both systolic and diastolic BP on non-dialysis days. In normotensive patients, MB increased BP during the first hour of dialysis and for 90 min on the non-dialysis day. The BP in the healthy controls remained unchanged. Plasma and platelet NO(2)+NO(3) (stable metabolites of NO) levels were determined. The NO(2)+NO(3) generation rate in the first post-dialysis day was calculated. The plasma and platelet NO(2)+NO(3) were higher in the hypotensive group than in the normotensive dialysis group. The generation rate of nitrates was higher (P<0.01) in the hypotensive group (1.21+/-0.13 micromol/min and 0.74+/-0.16 after MB) than in the normotensive patients (0.61+/-0.11 micromol/ min and 0.27+/-0.14 after MB). No side-effects were recorded.
Conclusions : MB is an efficient therapy in the prevention of dialysis hypotension.