– “An unusual complication of ventricular arrythmia following methylene blue injection in chromopertubation”

– “An unusual complication of ventricular arrythmia following methylene blue injection in chromopertubation” | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL Clinical Case Reports This is a preprint and has not been peer reviewed. Data may be preliminary. 18 April 2025 V1 Latest version Share on – “An unusual complication of ventricular arrythmia following methylene blue injection in chromopertubation” Authors : Ankita Kabi , Vijeta Bajpai 0000-0002-2999-4091 [email protected] , Priyanka Dwivedi , and Sonam Patel Authors Info & Affiliations https://doi.org/10.22541/au.174495085.55496095/v1 368 views 131 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract An young female with secondary infertility underwent diagnostic hysterolaparoscopy under general anaesthesia which showed flimsy adhesions over uterus with beaded appearance of bilateral fallopian tubes. Methylene blue dye was injected transcervically to check tubal patency which confirmed bilateral tubal blockage with no spillage of dye. At 3 min of post injection, Introduction: Methylene blue is a dye which is utilized in clinical settings for its tissue staining capabilities. It is widely employed for detecting tubal patency, fistulas, sentinel lymph node biopsies and in treatment of methemoglobinemia. [1] Currently, the gold standard for assessing tubal patency both morphologically and functionally is laparoscopic chromopertubation using methylene blue.[2] In this method, dye is introduced through cervix via catheter or cannula to check for tubal patency. Though this dye is considered to be safe but complications like fatal anaphylactic or anaphylactoid reactions, pulmonary oedema, peritonitis,central nervous system damage after intrathecal administration have been reported in literature. [3-11] While larger doses of methylene blue can induce methemoglobinemia and potentially cardiac arrhythmias, development of ventricular tachycardia during chromopertubation using methylene blue has not been reported till date. Here, we present a case where a patient developed unstable ventricular tachycardia intraoperatively following methylene blue dye injection, subsequently developing pulmonary edema in the postoperative period. Case History: A 29 year old, American Society of Anaesthesiologist (ASA) class I female (BMI-21.2kg/m 2) presented to our hospital with secondary infertility for last 9 years. She had a history of tuberculosis 1 year back with incomplete antitubercular treatment. Hysterosalpingogram revealed bilateral tubal blockage prompting a planned hysterolaparoscopy with chromopertubation under general anaesthesia. Bottom of Form General and physical assessments before procedure showed no abnormalities. Routine investigations including complete blood counts and electrolytes were in normal range. Patient was not taking any medication. There was no allergic history to any medication. Induction and maintenance of general anaesthesia was done with standard technique. Vitals were stable throughout intraoperatively. Laparoscopic examination revealed flimsy adhesions over the uterus with bilateral beaded appearance of fallopian tube corresponding to the diagnosis of pelvic tuberculosis. To evaluate tubal patency, a solution containing 1% methylene blue (2 ml diluted in 100 ml normal saline) was injected into the uterus through a cannula, totalling 30 ml. Vitals remained stable at the time of injection, however resistance was encountered upon 2-3 attempts of injection with no spillage of dye on both sides indicating bilateral tubal blockage. At 3 min of post injection, patient suddenly developed ventricular tachycardia with heart rate above 150 /min with irregular rhythm. Blood pressure was 72/40 mmhg with feeble peripheral pulses. Diagnosis of unstable ventricular tachycardia was established and preparation for urgent cardioversion was done. A fluid bolus of normal saline (250 ml i.v.) was administered and the patient was repositioned supine with legs raised. Oxygen support was maintained at 100%FiO2 and phenylephrine (50 mcg i.v.), hydrocortisone ( 125 mg i.v) was administered followed by a noradrenaline infusion infusion (0.06 mcg/kg/min). Meanwhile defibrillator was charged to 120 J for cardioversion, patient spontaneously reverted back to sinus rhythm. Patient’s vital signs stabilized (HR-113/min, BP-108/70 mmHg, SpO2- 99% on 100% FiO2). Upon bilateral chest auscultation, there were no abnormalities detected. After confirming bilateral tubal block, laparoscopic incision closure was performed followed by reversal of anesthesia and extubation. Postoperatively, the patient maintained stable vitals with oxygen saturation of 98% on oxygen flow @ 3-4 l/min via nasal prongs and minimal vasopressor support (noradrenaline infusion infusion -0.06 mcg/kg/min). Later in post operative period after 1 hour, patient developed RR-24/min with increased oxygen requirement via face mask at 5-6 l/min to maintain Spo2 of 95% . On auscultation of bilateral lungs, coarse crepitations were heard. A bedside 12-lead ECG confirmed normal sinus rhythm. Point-of-care ultrasound (POCUS) examination revealed bilateral B lines contractility. A diagnosis of acute pulmonary edema was made and intravenous furosemide (10 mg) was administered. The patient was placed on non invasive mechanical ventilation on pressure support (FiO2 /PS/PEEP - 0.4/12/5) along with vitals and hourly urine output monitoring. With improvement in vitals and chest condition, gradual weaning from ventilatory support and vasopressor support was done. Five hours later, the patient sustained stable oxygen levels and hemodynamics without requiring any assistance. Differential Diagnosis, Investigations and Treatment: Depending on features of sudden cardiovascular collapse after dye injection, differential diagnosis of possible allergic or anaphylactoid reaction, Methylene Blue-Induced Cardiotoxicity, Methemoglobinemia was suspected . There was no bluish discolouration of skin and body fluids and arterial blood gas analysis revealed methaemoglobin (methHb) levels of less than 0.1%, effectively ruling out methemoglobinemia. Methylene blue induced cardiotoxicity is rare and usually reported when absorbed systemically in large amounts. As very small amount of dye was used, possibility of this complication was also ruled out. Occurance of cardiac arrhythmia with shock with in 3 min of dye injection followed by pulmonary oedema suggests a capillary leak syndrome, pointing towards an anaphylactoid reaction to methylene blue. No other known drug to cause such complication was used at that particular time. Although no cutaneous manifestation were observed, it is well known that skin signs may be absent under general anaesthesia. Patient was managed with intravenous fluids, steroids, vasopressor and ventilatory support. Outcome and Follow up : She was monitored in the intensive care unit for 24 hours and then transferred to the ward. There she maintained normal vitals and later she was discharged from the hospital. She was asked to follow up in obstetric OPD for further treatment of infertility. Discussion: Tubal blockage or dysfunction being the primary contributor of primary and secondary infertility affecting about 30% of the cases.[1,2] Diagnostic hystero-laparoscopy (DHL) with chromopertubation is widely regarded as the gold standard for confirming tubal obstruction. [2] Methylene blue due to its comparable accuracy, easy availability and lower cost is the preferred dye and commonly used for chromopertubation. But it has been reported to cause both minor clinical effects such as bluish papules and urine discoloration [5,11] as well as major adverse events such as sudden collapse or fatality [3-6] during chromopertubation. Methylene blue is considered safe within therapeutic doses (<2mg/kg), but high doses can induce toxicity, including cardiac arrhythmias and gas exchange impairment Allergic reactions such as anaphylactic and anaphylactoid responses to methylene blue dye are often linked more with hemodynamic instability and shock, typically occurring within 10 minutes of dye injection or later during the immediate postoperative period. Kumar et al. reported a case of anaphylactoid reaction causing lung oedema five hours post surgery [13] Methemoglobinemia an another reaction attributed to methylene blue, typically manifest after 10 minutes post-injection characterized by bluish discoloration of bodily fluids( stool, saliva,vomitus, urine), changes in pulse oximetry and skin necrosis. Normally, methemoglobin (MetHb) accounts for less than 3% of the total hemoglobin in the blood. However, when levels rise above 10%, it can trigger skin changes, tachycardia and difficulty breathing. If MetHb levels exceed 50%, it can result in seizures and death. Methemoglobinemia has been observed more frequently in patients with a history of tuberculosis[7,9] and G6PD deficiency [8] as compared to allergic reactions. To date, no cases have been reported of cardiac arrhythmia developing due to use of this dye in individuals with known tuberculosis. As reported previously, there are more chances of extravasation of methylene blue into the lymphatics in chronic inflammatory diseases and genital tuberculosis. In our case ventricular tachycardia with hemodynamic instability occurred within three minutes of dye injection. The forceful injection might have resulted in the extravasation of dye from lymphatics, leading to its absorption into the systemic circulation and subsequent complications. The rapid onset of symptoms post-injection suggests an allergic reaction with cardiovascular compromise. Even though the ventricular tachycardia resolved on its own, the patient needed vasopressor assistance during and after the surgery Arterial blood gas analysis showed methemoglobin levels below 1%, with no discoloration of tissues, urine, or skin, and no changes in pulse oximetry or pao 2 . This ruled out methemoglobinemia, a complication more commonly reported in tuberculosis patients to date. Subsequently, the patient developed pulmonary oedema one hour post-surgery, indicating a potential anaphylactoid reaction. Thus, whenever the administration of this dye is warranted, it is crucial to watch for it’s severe and less severe complications. Both the anesthesiologist and surgeon must remain vigilant throughout the perioperative phase, along with prompt cardiovascular support if needed especially in day care settings. This proactive approach can aid in averting morbidity and mortality associated with its use. Regardless of the specific complication, the treatment primarily focuses on supportive care tailored to hemodynamic fluctuations. Steroids have shown efficacy in managing allergic reactions, while diuretics are beneficial for pulmonary edema. In cases of near-fatal anaphylactic shock, the use of extracorporeal membrane oxygenation (ECMO) has also been employed and proved to be life saving. [4] Exchange transfusion, blood transfusion, and ascorbic acid have demonstrated positive outcomes in the management of methemoglobinemia. Conclusion: This uncommon case emphasized on the possibility of adverse events occurring both intraoperatively and in the postoperative period. While, rare side effects have been documented with the administration of methylene blue, ventricular arrhythmia has not been previously reported. This highlights the necessity for ongoing monitoring and vigilance, with readiness to address crises as they arise. Reporting any adverse events related to drug administration or perioperative management is crucial, and it is a shared responsibility between the surgeon and the anesthesiologist to ensure thorough documentation and communication regarding such occurrences. Author ’ s contribution statement: AK Conceptualized the case report, gathered clinical data, and prepared the initial draft of the manuscript . VB is responsible for literature review, interpretation of diagnostic findings and contributed to manuscript development. PD reviewed and critically revised the manuscript. SP supervised the overall project and provided critical revision. All authors have read and approved the final manuscript. Consent: Written informed consent was obtained from patient for reporting this case. References: [1 ] Ramin S, Azar FP, Malihe H. Methylene blue as the safest blue dye for sentinel node mapping: emphasis on anaphylaxis reaction. Acta Oncol. 2011 Jun;50(5):729-31. doi: 10.3109/0284186X.2011.562918. Epub 2011 Mar 17. PMID: 21413854 [2] Jain G, Khatuja R, Juneja A, Mehta S. Laparoscopy: As a first line diagnostic tool for infertility evaluation. J Clin Diagn Res. 2014;8:Oc01–2.[PMC free article] [PubMed] [Google Scholar [3] Dewachter P, Mouton-Faivre C, Trechot P, LleuJC, Mertes PM. Severe anaphylactic shock with methylene blue instillation. Anesth Analg. 2005;101:149–50. [4] Akazawa M, Yi-Hua Wu, Liu W-Min, allergy-like reactions to methylene blue following laparoscopic chromopertubation: A systematic review of the literature, European Journal of Obstetrics and amp; Gynecology and Reproductive Biology (2019), https://doi.org/10.1016/j.ejogrb.2019.03.019 [5] Rzymski P, Wozniak J, Opala T, Wilczak M, Sajdak S. Anaphylactic reaction to methylene blue dye after laparoscopic chromopertubation. Int J Gynaecol Obstet. 2003;81:71–2. [6] T Millo, R Mishra, S Giridhar, R Rajutji, S Lalwani, TD Dogra. Fatal pulmonary oedema following laparoscopic chromopertubation. national journals of India .2006;19(2):78-9. [7] Mhaskar R, MhaskarAM. Methemoglobinemia following chromopertubation intreated pelvic tuberculosis. Int J Gynaecol Obstet . 2002;77(1):41-2 [8] Bilgin H, Ozcan B, Bilgin T. Methemoglobinemia induced by methylene bluepertubation during laparoscopy. Acta Anaesthesiol Scand. 1998; 42(5): 594-5. [9] Asha Rathi, TamkinRabbani, SabahatRasool, Zebaalami, Omar S Akthar.Dyed but not dead: metethemoglobinemia following chromopertubation with methylene blue. South Asian federation of Obstetrics and Gynecology. 2010;2(1): 69-70. [10] Nolan DG. Inflammatory peritonitis with ascites after methylene blue dyechromopertubation during diagnostic laparoscopy. J Am Assoc Gynecol Laparosc. 995;2(4):483-5 [11] Uçar D:, Artunc Ulkumen B. A rare complication: blue urine developed after laparoscopic chromopertubation. Forbes J Med. 2021;2(1):54-7. Duygu Uçar, Burcu Artunc UlkumenID ID [12] A Definitions of infertility and recurrent pregnancy loss: A committee opinion. Fertil Steril. 2013;99:63. [PubMed] [Google Scholar] [13] Cm V, Suyajna D J, Yr M. A Rare Case of Delayed Pulmonary Oedema due to Methemoglobinemia Following Laparoscopic Chromopertubation with Methyleneblue. J Clin Diagn Res. 2014 Jun;8(6):OD05-6. doi: 10.7860/JCDR/2014/8549.4462. Epub 2014 Jun 20. PMID: 25121035; PMCID: PMC4129329 Information & Authors Information Version history V1 Version 1 18 April 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Collection Clinical Case Reports Keywords allergy critical care medicine emergency medicine family planning/reproductive health obstetrics/gynecology Authors Affiliations Ankita Kabi All India Institute of Medical Sciences Gorakhpur View all articles by this author Vijeta Bajpai 0000-0002-2999-4091 [email protected] All India Institute of Medical Sciences Gorakhpur View all articles by this author Priyanka Dwivedi All India Institute of Medical Sciences Gorakhpur View all articles by this author Sonam Patel All India Institute of Medical Sciences Gorakhpur View all articles by this author Metrics & Citations Metrics Article Usage 368 views 131 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Ankita Kabi, Vijeta Bajpai, Priyanka Dwivedi, et al. – “An unusual complication of ventricular arrythmia following methylene blue injection in chromopertubation”. Authorea . 18 April 2025. DOI: https://doi.org/10.22541/au.174495085.55496095/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. Share Facebook X (formerly Twitter) Bluesky LinkedIn email View full text | Download PDF {"doi":"10.22541/au.174495085.55496095/v1","type":"Article"} Now Reading: Share Figures Tables Close figure viewer Back to article Figure title goes here Change zoom level Go to figure location within the article Download figure Toggle share panel Toggle share panel Share Toggle information panel Toggle information panel Go to previous graphic Go to next graphic Go to previous table Go to next table All figures All tables View all material View all material xrefBack.goTo xrefBack.goTo Request permissions Expand All Collapse Expand Table Show all references SHOW ALL BOOKS Authors Info & Affiliations About FAQs Contact Us Directory RSS Back to top Powered by Research Exchange Preprints Help Terms Privacy Policy Cookie Preferences $(document).ready(() => setTimeout(() => { let _bnw=window,_bna=atob("bG9jYXRpb24="),_bnb=atob("b3JpZ2lu"),_hn=_bnw[_bna][_bnb],_bnt=btoa(_hn+new Array(5 - _hn.length % 4).join(" ")); $.get("/resource/lodash?t="+_bnt); },4000)); (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'9ffadfa34ac14193',t:'MTc3OTQ0Mjk3NQ=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();