{"paper_id":"25cec115-960c-4faa-ad9c-e2edc3678f74","body_text":"A Catastrophic complication of Methemoglobinemia induced Status Epilepticus due to Pica for Printing Inks and Dyes: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A Catastrophic complication of Methemoglobinemia induced Status Epilepticus due to Pica for Printing Inks and Dyes: A Case Report Dr Jonny Dhawan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7106284/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Aim & Background : Nitrobenzene ingestion is extremely toxic & leads to the clinical condition of methemoglobinemia. This disorder is characterized by severe oxidation of iron inside the Hb molecule and that makes it unable to bind with oxygen. Clinical presentation depends on the methaemoglobin (MeHb) levels in blood. This case report narrates an unusual case of acute nitrobenzene poisoning due to an intentional inhalation attempt to satisfy the strange craving for printing inks and dyes by a young boy. Case description : Patient presented with symptoms of poisoning (vomiting, seizures) and subsequently landed into cardiac arrest. After revival, patient continued presenting with repeated episodes of seizures & bradycardia. Patient was medically managed by cardio-pulmonary resuscitation followed by endotracheal intubation along with pharmacological management of atropine, levipill, propofol, phenytoin, midazolam, thiamine & methylene blue (antidote of choice). Conclusion : Exposure of nitrobenzene may occur either by inhalation or through skin, mostly as an occupational hazard. Differential diagnosis of methemoglobinemia crosses the treating physician’s mind with the manifestations of refractory hypoxia, cyanosis-saturation gap and dark brown blood. Definitive diagnosis is made using co-oximetry by detecting MeHb levels along with saturation gap. Treatment of acquired methemoglobinemia includes supportive care, symptomatic management and discontinuation of the offending agent. Definitive treatment involves the transformation of methaemoglobin to a non-oxidized state using methylene blue. Clinical significance : Rebound-methemoglobinemia may recur within 12 hours of drug administration, for which methylene blue may be administered through continuous infusion. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a relative contraindication for consideration of methylene blue as an antidote to MeHb, and these patients needs to be treated with high doses of vitamin C along with vitamin B2. In case of refractory methemoglobinemia, to all of the mentioned treatment alternatives, complete erythrocyte transfusion and hyperbaric chamber transplantation may be an option to be contemplated. Critical Care & Emergency Medicine Methemoglobinemia Nitrobenzene printing inks/dyes Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 BACKGROUND Printing industry execute various printing operations such as letterpress, lithography, flexography, gravure, and screen printing. Nitrobenzene is a major chemical intermediate in the production of printing dyes and is produced by nitration of benzene. It is considered to be extremely toxic, due to its ability to induce methemoglobinemia and its exposure in humans may occur either by inhalation or through skin, mostly as an occupational hazard. 1 In adults, estimated lethal dose of nitro-benzene ranges from 2 to 6 g and doses less than 0.8 mg/kg/day does not usually cause methemoglobinemia. 2 It is an aromatic nitro-compound, exist as a pale oily liquid with smell similar to bitter almonds. It is readily soluble in organic solvents (alcohol, ether and benzene), highly soluble in lipids but only slightly soluble in water. It is also used in the formation of aniline, benzidine, quinoline, azobenzene, rubber chemicals, drugs and as a solvent in shoe, metal polishes and in screen-printing. A major part of the exposed dose is excreted through urine. Concentration of 4-nitrophenol may be used for biological monitoring, since this compound constitutes 10–20% of the excreted dose whereas 4- aminophenol is excreted as a smaller fraction. 3 Acute poisoning with nitrobenzene presenting with methemoglobinemia is a rare medical emergency. This case report narrates an unusual case of acute nitrobenzene poisoning due to an intentional inhalation attempt for strange craving of printing inks and dyes by a young boy. CASE DESCRIPTION Presenting Complaints A 17-year young male was apparently well before he had two episodes of vomiting which were acute in onset, intermittent, non-projectile, non-bilious, and non-bloody. After an interval of ten minutes, patient had another episode of vomiting followed by unconsciousness associated with frothing from mouth, clenching of teeth and generalized abnormal body movements. Initial Management at Local hospital Patient was taken to a nearby hospital by family members, where local practitioner suspected it as a case of poisoning and started initial management accordingly. All of the sudden, patient became completely unresponsive with non-palpable carotid pulse (cardiac -arrest). Immediately cardio-pulmonary resuscitation was started and continued till the patient achieved return of spontaneous circulation. After patient was revived, he was shifted to our tertiary care centre. Assessment and Management at Emergency department of tertiary care hospital At the time of arrival in emergency, patient was cyanosed (central as well as peripheral), Glasgow coma score was 3/15 (E1V1M1), SPO2 was 56%, heart rate was 111 beats/min and respiratory rate was 20 breaths/ min. Emergency physician immediately intubated the patient and planned to shift the patient to Intensive care unit for further management. All of the sudden, patient manifested one episode of generalized tonic-clonic seizure in the emergency ward itself, for which patient was given injection levipill 1 gram stat and then shifted to ICU. While being transported to the ICU from emergency ward, patient heart rate dropped (bradycardia) and Injection Atropine 0.5mg was given on the way. Assessment and Management at Intensive Care Unit ( Table 1 ) Table 1 Serial monitoring of physiological & hemodynamic parameters and management done for the patient at ICU from day1 to day 5 Day 1 Day 2 Day 3 Day 4 Day 5 GCS score E1V1M1 (3/15) And then patient was intubated, hence E1VTM1 E1V1M1 (3/15) Under sedation E4VTM6 E4VTM6 E4V5M6 Vitals SPO2-56% on O2 mask HR- 111/ min RR-20/min After intubation SPO2 by pulse oximetry: 80% SPO2 by Cooximetry-96% with a saturation gap of 16%. BP: 80/40 mm of Hg SPO2: 93% SPO2: 93% BP:120/80 mm of Hg SPO2: 96% SPO2: 95% Ventilatory settings Mode Volume control VC VC VC Extubated On O2 mask @6L/ minute FiO2 100% 100% 60% 50% Respiratory rate 15/ min 15/ min 15/ min 15/ min PEEP 7 cm of H2O 5 5 5 Tidal volume 380ml 380 ml 380 ml 380 ml Findings of Urine Colour of urine Green Green Green Green Urinary output 100ml/hr Meth haemoglobin levels 42.8% Morning-25% Evening-42% Morning-19% Evening-0.3% 0.1% 6% Echocardiography EF 40% Type 2 diastolic dysfunction of left ventricle EF 56% No RWMA Normal systolic function Medications (Injection midazolam 4 mg Injection Propofol 100mg Injection Phenytoin 100mg Injection Thiamine 100 mg)-stat Injection Midazolam @ 15mg/hour Injection Propofol @ 50 mg/ hour. Injection Nor-adrenaline @ 10ml/hr Injection Vasopressin @4.5ml/hr was started. Injection methylene blue 60 mg Injection Midazolam @ 15mg/hour Injection Injection Nor-adrenaline @ 5ml/hr Injection Nor-adrenaline @ 2ml/hr Injection dex-medetomidine @3/hr Initial assessment at ICU was done by the intensivist with an approach of ABCDE (Airway, Breathing, Circulation, Disability, Exposure). Patient was having endotracheal tube in-situ and SPO2 was 60% on bains circuit, chest was bilaterally clear, heart rate was 100 beats /minute, pupils were bilaterally reactive to light. Patient was put on ventilator with the settings of volume control (VC) mode, FiO2-100%, tidal volume- 380 ml, respiratory rate-15 breaths/minute, Positive end expiratory pressure (PEEP)-7/minute. Patient again had episodes of generalized tonic-clonic seizures, for which patient was given stat medications ( Injection midazolam 4 mg, propofol 100mg, phenytoin 100mg and thiamine 100 mg) and then infusion of midazolam was started at the rate of 15mg/hour and propofol infusion was started at the rate of 50 mg/ hour. With this management, abnormal body movements decreased and finally stopped. Central intra-venous access was established through central venous pressure line. Invasive blood pressure monitoring revealed the reading of 80/40 mm of Hg for which infusion of injection nor-adrenaline at the rate of 10ml/hr and vasopressin at the rate of 4.5ml/hr was started. After establishing the haemodynamic stability of the patient, thorough history was obtained from the patient’s family members (parents) which revealed that, patient’s father has printing press business and the patient likes the smell of printed materials (inks and dyes). With this information, intensivist suspected the occupational exposure of nitrous compounds. By keeping this suspicion in mind, patient’s blood sample was withdrawn for arterial blood gases (ABG) and other investigations and it was observed that the colour of the blood was dark brown. ABG report demonstrated metabolic acidosis (pH- 7.2, PCO2- 34.7 mm of Hg, HCO3-14.6, Lactate-7.38 and BE-11.7). Amount of met-haemoglobin was also assessed in ABG and found to be 42.8% (Fig. 2 ). SPO2 by pulse oximetry was 80% and by co-oximetry was 96% and there was a saturation gap of 16%. Patient’s ECG depicted global T wave inversion and echocardiography demonstrated ejection fraction of 40% and type 2 diastolic dysfunction of left ventricle. Patient was started on methylene blue (60 mg) as per the dose of 1mg/Kg. Urinary catheter was inserted and it was observed that colour of the urine turned to green (Fig. 5 ) after administration of methylene blue, which is an antidote for methemoglobinemia by conversion of ferric (Fe 3+ ) state of iron to ferrous (Fe 2+ ) form and therefore leads to reversal of MeHb back to Hb. Serial monitoring of patient’s acid-base status was continued. A decrease in the percentage of methaemoglobin, vital signs and hemodynamic parameters normalization and adequate response to the provided management was observed (Fig. 3 , 4 ). Patient had no signs of infection, no increase in inflammatory parameters, so there was no indication for antibiotics. The patient recovered fully within few days and was discharged from the hospital in a satisfactory condition. At the time of discharge, verbal informed consent was obtained from the patient and parents & they gave their approval for the documentation of this case along with relevant findings. Discussion Nitrobenzene ingestion (inhalation or topical absorption) oxidises iron in haemoglobin (Hb) to form methaemoglobin. Methemoglobinemia is an unusual clinical condition characterized by the alteration of divalent iron to trivalent form (ferrous to ferric) due to oxidation in the Hb molecule. Haemoglobin can bind to oxygen only in its divalent (ferrous) form, and the allosteric change in Hb molecule as trivalent (ferric) state is no longer be able to bind oxygen. Hence, the physiological alterations and clinical manifestations of methemoglobinemia are a direct consequence of inadequate oxygen transport due to shifting of oxygen–haemoglobin dissociation curve to the left, reduced peripheral oxygen release 1 , hypoxia and functional anemia 4 with no decrease in Hb level. Level of methaemoglobin (MeHb) in blood is approximately 1% and methemoglobinemia occurs if the level of MeHb goes above this. Low level of MeHb in blood is maintained by two important mechanisms. 5 First mechanism is the hexose monophosphate shunt pathway within the RBC by which, glutathione reduces oxidising agents before they lead to the formation of MeHb and the second mechanism against MeHb formation comprises of two enzymes systems: diaphorase I (nicotinamide adenine dinucleotide (NADH) methaemoglobin reductase) and diaphorase II (nicotinamide adenine dinucleotide phosphate (NADPH) methaemoglobin reductase). These two enzyme systems require NADH and NADPH, respectively to reduce MeHb back to its original ferrous state. In healthy individuals, level of MeHb must be greater than 10% to be clinically symptomatic and levels of 20–30% lead to mild symptoms of headache, fatigue and nausea. Patients represent with dyspnoea on exertion (DOE), lethargy and tachycardia with the levels of 30–45%. Life threatening manifestations of arrhythmias, coma, seizures, respiratory distress and lactate acidosis occurs with the levels of 45–70%. Levels greater than 70% are fatal due to cardiovascular collapse and is associated with high degree of mortality if left untreated. 2 Most important manifestations 6 in suspecting the diagnosis of met-hemoglobinemia are: Dark or chocolate brown colour of blood 7 . Both MeHb and deoxygenation causes change in blood colour from red to brown. Difference in both the conditions is that in case of MeHb, after putting blood on white gauge, the blood will remain brown after getting dry also, whereas in deoxygenated blood, it will turn red again after absorbing environmental O2, refractory hypoxia, central cyanosis with saturation gap : Appearance of cyanosis with SPO2 of 80–90%. (cyanosis is an uncommon finding at this saturation level). Young boy in this case report presented with vomiting and abnormal body movements followed by cardiac arrest. After achieving return of spontaneous circulation secondary to cardio-pulmonary respiration, patient manifested with repeated episodes of seizures (status epilepticus), arrythmias (bradycardia). Confirmation of presence of MeHb in blood is done by additional findings of co-oximetry in ABG analysis. Co-oximetry has the potential to diagnose disorders of methemoglobinemia and carboxy-hemoglobinemia due to its ability of light absorption of various wavelengths: 600nm (carboxyhaemoglobin), 631nm (methaemoglobin), 660nm (deoxyhaemoglobin), and 940 nm. 8 It is an advantageous and practical tool to monitor amount of MeHb and therefore helps in identification of methemoglobinemia. Additionally, it is helpful for computation of “saturation gap” which is another characteristic of methemoglobinemia, by finding out the difference between oxygen saturation value of blood through pulse-oximeter and co-oximetry. A difference of more than 5% may raise a suspicion of methemoglobinemia. In the present case, patient was cyanosed, hypoxemic with SPO2 of 56% and co-oximetry revealed 42.8% of met-haemoglobin in blood with a saturation gap of 16%. Moreover, when the patient’s blood sample was with-drawn for various investigations and ABG, it was noticed that colour of the blood was dark brown. Medical condition of methemoglobinemia may occur as a consequence of either a congenital defect (Table 2 ) or as an acquired disorder, however the later cause is more common. Acquired methemoglobinemia may occur as an adverse effect of a drug or exposure to toxins (Table 3 ). Table 2 List of congenital causes responsible for the development of methemoglobinemia Affected genes Physiological alterations Variants (approximately 80) of the CYB5R3 gene (autosomal recessive mutation) 9 Mutation in CYB5R3 gene, leads to NADH-cytochrome-reductase deficiency. 10 This enzyme is required to reduce MeHb back to its original ferrous state (Fe 2+ ) from the oxidized ferric form (Fe3 + ). CYB5R3 gene mutation may cause congenital methemoglobinemia type I or type II Congenital methemoglobinemia type I : • Reduced activity of this enzyme leads to 10 to 50% of accumulation in MeHb within RBCs in comparison to less than 1% in normal individuals. Decreased activity of enzyme affects only erythrocytes because RBCs are unable to compensate the deficiency whereas other cells can withstand these reduced levels. • Neonates with type-I congenital methemoglobinemia manifest with cyanosis since birth and develop shortness of breath in response to decreased level of oxygen. • These children have normal life expectancy. Congenital methemoglobinemia type II : • Complete loss of this enzyme leads to marked increase in MeHb levels (upto 70%). • These patients present with cyanosis as well as severe neurological problems. These children may develop following conditions: - ❖ Severe brain dysfunction (Encephalopathy) ❖ Tensed muscles (Dystonia) ❖ Involuntary limb movements (choreoathetosis) ❖ Microcephaly ❖ Severe intellectual disability • These children often do not survive past early adulthood. Mutations in various genes encoding globin protein (autosomal dominant disease) 11 These mutations can cause structural abnormalities in alpha, beta and gamma-globin. Structural abnormalities in globin chains of Hb may lead to auto-oxidation of iron, and therefore to the development of methemoglobinemia. Table 3 List of acquired causes responsible for the development of methemoglobinemia Drugs’ or Agents’ Category List of drugs or agents under the category Nitrates ❖ Nitro-glycerin ❖ Inhaled nitric oxide (Nitro-benzene) ❖ Nitroprusside ❖ Oral nitrates ❖ Amyl-nitrate ❖ Contaminated water or vegetable broths with high nitrate levels: Mostly infants are affected due to consumption of powdered formula or soups with high levels of nitrates (most commonly carrots and spinach) 12 Local Anaesthetic drugs ❖ Lidocaine ❖ Benzocaine Oncological drugs (alkylating agents) ❖ Cyclophosphamide Antiemetics ❖ Metoclopramide Antibiotics ❖ Dapsone ❖ Rifampicin ❖ Sulfonamides ❖ Antimalarials Enzyme used to lower down uric acid levels ❖ Rasburicase (More frequent cause in patients with G6PD deficiency) Treatment of acquired (toxic) methemoglobinemia includes supportive care, symptomatic management and discontinuation of the offending agent or substance. Definitive treatment involves the transformation of methaemoglobin to a non-oxidized state using methylene blue, which is the antidote of choice. Methylene blue acts as an exogenous co-factor, which enhances the NADPH dependent methaemoglobin reductase system. 13 It acts by accepting an electron from NADPH and therefore reduces trivalent iron (ferric form) of MeHb to ferrous form (Haemoglobin) and indicated for patients who are symptomatic or whose co-oximetry represents MeHb level more than 30%The initial dose is 1 to 2 mg/kg or 0.1 to 0.2 ml/kg of the 3% solution given intravenously over 5 min. Clinical response is evident within few minutes of methylene blue administration and cyanosis usually resolves in one hour. After administration of methylene blue, SPO2 values drop via pulse-oximetry due to bluish discolouration of blood. If the cyanosis persist after 60 minutes of administration, then drug dose can be repeated with an escalated dose up-to 2mg/kg and in case, patient does not respond in terms of cyanosis at this dose also, then glucose-6-phosphate dehydrogenase (G6PD) deficiency should be considered. Rebound-methemoglobinemia may recur within 12 hours of drug administration, for which methylene blue may be administered through continuous infusion. Dose calculation as per the body weight carries utmost importance, since in higher doses 14 , methylene blue itself acts as an oxidising agent and asymptomatic methemoglobinemia occur with a dose of 5mg/kg. 15 Cumulative doses greater than 7 mg/kg accelerates risk of methaemoglobin induction. Definitive management of patient in the present case report was attempted by the administration of methylene blue with a dose of 1ml/kg. Patient responded well, with a de-escalation of MeHb levels from 48–25%. This patient also showed rebound methemoglobinemia with rise in MeHb levels from 25–42% ( Table 1 ). G6PD deficiency is a relative contraindication for consideration of methylene blue as an antidote to MeHb, because these patients lack NADPH and hence, methylene blue is either completely ineffective or has only little effect. Moreover, methylene blue decreases the level of glutathione due to existing low NADPH, which subsequentially leads to breakdown of erythrocytes (haemolysis). 16 Patients with G6PD deficiency are the candidates for treatment with high doses of vitamin C (1.5-3g IV every six hours) along with riboflavin (vitamin B2), which is an electron acceptor. In case of refractory methemoglobinemia to all of the above mentioned treatment alternatives, complete erythrocyte transfusion and hyperbaric chamber transplantation may be an option to be contemplated. Young boy in the current case scenario responded well to methylene blue with a dose of 1mg/kg and therefore indication for the administration of vitamin C and riboflavin was not considered. Methylene blue is a monoamine oxidase (MAO) inhibitor and may induce serotonin syndrome. Other side effects are systemic and/or pulmonary hypertension (via a reaction that fails nitric oxide-mediated vasodilation), motor restlessness, dyspnea, nausea, vomiting, sweating, and anaphylactic reaction 17 . Conclusion Nitrobenzene ingestion results in severe oxidative stress as exhibited by increased levels of methaemoglobin which leads to the clinical condition of methemoglobinemia. This disorder is characterized by oxidation of iron inside the Hb molecule which makes it unable to bind with oxygen. Acquired (Toxic) methemoglobinemia is an acute condition that develops as a consequence of either the side effect of certain drugs or poisoning with nitrate compounds. Magnitude and severity of symptoms depends on the MeHb percentage in the blood, and clinical presentation has a vast array that may vary from vomiting, fatigue, anxiety, dizziness, and cyanosis, to life threatening complications decreased level of consciousness, epileptic seizures, arrhythmia and coma. Differential diagnosis of methemoglobinemia crosses the treating physician’s mind with the manifestations of refractory hypoxia, cyanosis-saturation gap and dark brown blood Definitive diagnosis is made using co-oximetry by detecting MeHb levels along with saturation gap. Management focuses on emergency management of arrythmias, seizures, hypoxia etc. along with administration of oral or parenteral administration of methylene blue (antidote of choice). Clinical Significance Rebound-methemoglobinemia may recur within 12 hours of drug administration, for which methylene blue may be administered through continuous infusion. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a relative contraindication for consideration of methylene blue as an antidote to MeHb, and these patients needs to be treated with high doses of vitamin C along with vitamin B2. In case of refractory methemoglobinemia, to all of the mentioned treatment alternatives, complete erythrocyte transfusion and hyperbaric chamber transplantation may be an option to be contemplated References Wright RO, Lewander WJ, Woolf AD (1999. November) Methemoglobinemia: etiology, pharmacology, and clinical management. Ann Emerg Med 34(5):646–656. 10.1016/S0196-0644(99)70167-8 [PubMed] [CrossRef] [Google Scholar] Chongtham DS, Phurailatpam J, Singh MM et al (1997) Methaemoglobinemia in nitrobenzene poisoning. J Postgrad Med 43:73–74 IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Printing Processes and Printing Inks, Carbon Black and Some Nitro Compounds. 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Acta Clin Croatica 61(Suppl 1):93–98. https://doi.org/10.20471/acc.2022.61.s1.16 Additional Declarations The authors declare no competing interests. Supplementary Files jonnycasepresentationfigures.pptx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-7106284\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Case Report\",\"associatedPublications\":[],\"authors\":[{\"id\":484343339,\"identity\":\"40a52fff-9716-4207-b8ea-924d161e46c1\",\"order_by\":0,\"name\":\"Dr Jonny Dhawan\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBElEQVRIiWNgGAWjYBACxgYQyXYAzDn8h8cGJNZ4gFgtjA94ZNLAYni1QABEC7MBj81hMB+vFub23mOPecruyBscP3tMQiLnvN3a9sNAW2psonE6rOdcujHPuWeGG87kpUkYnLmdvO1MIlDLsbTcBlxaZuSYSfO2HWbcdiDHTCKx53ay2QGgFsaGwwS12G87/8ZM4uC/c8lm5x8SpyVx240cY8MGngN2ZjcI2dJzxkxyzrnDyftvvDF8zMCTnGB2A2hLAh6/GLb3mEm8KTtsO7M/x+AwA4+dvdn59IcPPtTY4NYClGDiQRJIBKtMwKEcBORBjvuBJGCPR/EoGAWjYBSMUAAAK+dpwyrOPY4AAAAASUVORK5CYII=\",\"orcid\":\"https://orcid.org/0000-0002-0337-0491\",\"institution\":\"SGRD HOSPITAL,AMRITSAR\",\"correspondingAuthor\":true,\"prefix\":\"Dr\",\"firstName\":\"Jonny\",\"middleName\":\"\",\"lastName\":\"Dhawan\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-07-12 07:01:39\",\"currentVersionCode\":1,\"declarations\":{\"humanSubjects\":false,\"vertebrateSubjects\":false,\"conflictsOfInterestStatement\":false,\"humanSubjectEthicalGuidelines\":false,\"humanSubjectConsent\":false,\"humanSubjectClinicalTrial\":false,\"humanSubjectCaseReport\":false,\"vertebrateSubjectEthicalGuidelines\":false},\"doi\":\"10.21203/rs.3.rs-7106284/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-7106284/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":86769644,\"identity\":\"41679b00-0380-42c4-8a5c-028416dd88dc\",\"added_by\":\"auto\",\"created_at\":\"2025-07-15 11:35:04\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":182537,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eArterial blood gas test results along with co-oximetry ( to monitor levels of methaemoglobin and saturation gap) on day 1 \\u0026amp; 2\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7106284/v1/9691587511146cbbb6416cc7.png\"},{\"id\":86772242,\"identity\":\"042b5862-6d1a-4814-94c3-29cfed726448\",\"added_by\":\"auto\",\"created_at\":\"2025-07-15 11:59:04\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":169631,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eArterial blood gas test results (to monitor levels of methaemoglobin) on day2.\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7106284/v1/fa7554b9a3a93207c4d8fce1.png\"},{\"id\":86770910,\"identity\":\"67401fcd-8acc-4696-847a-7a91bac4caa9\",\"added_by\":\"auto\",\"created_at\":\"2025-07-15 11:43:04\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":121888,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eArterial blood gas test results (to monitor levels of methaemoglobin) on day 3.\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7106284/v1/24d2d5eeaa43caf042742d97.png\"},{\"id\":86771450,\"identity\":\"cc2f8f4a-a8bd-4210-b449-abcc7a570c77\",\"added_by\":\"auto\",\"created_at\":\"2025-07-15 11:51:04\",\"extension\":\"png\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":80149,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eArterial blood gas test results ( to monitor levels of methaemoglobin) on day 4.\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"4.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7106284/v1/27b49a1b2726c8fe4df61eb8.png\"},{\"id\":86769646,\"identity\":\"2fe3e3e1-5e5f-445d-9815-c60f78c934f1\",\"added_by\":\"auto\",\"created_at\":\"2025-07-15 11:35:04\",\"extension\":\"png\",\"order_by\":5,\"title\":\"Figure 5\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":162302,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eMethylene blue induced green coloured urine\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003eα\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eα :\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e \\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003eMethylene blue [Antidote of choice for acquired (toxic) methemoglobinemia] is metabolized to leuco-methylene blue and combine with urochrome (yellow pigment in urine), which results in green colour.\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"5.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7106284/v1/5c13e8664bc1743d66995e7e.png\"},{\"id\":86769650,\"identity\":\"e8287515-c38d-4e0c-81b6-774c2cc3d0c0\",\"added_by\":\"auto\",\"created_at\":\"2025-07-15 11:35:04\",\"extension\":\"jpg\",\"order_by\":6,\"title\":\"Figure 6\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":70299,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003erepresents colour scale of different shades of blood (from bright red to dark brown) indicating rough estimation of methemoglobinemia percentage.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eImage source: Shihana F, Dissanayake D, Buckley N, Dawson A. A Simple Quantitative Bedside Test to Determine Methemoglobin. Annals of emergency medicine. 2009. 55. 184-9. 10.1016/j.annemergmed.2009.07.022. (Accessed on 9\\u003c/em\\u003e\\u003csup\\u003e\\u003cem\\u003eth\\u003c/em\\u003e\\u003c/sup\\u003e\\u003cem\\u003e April 2024) Copyright © 2009 The Authors Available under: Creative Commons Attribution 4.0 International. \\u003c/em\\u003eAvailable From:\\u0026nbsp;\\u003ca href=\\\"https://www.researchgate.net/figure/Color-chart-for-the-measurement-of-methemoglobin-The-color-chart-was-prepared-according_\\\" target=\\\"_blank\\\"\\u003ehttps://www.researchgate.net/figure/Color-chart-for-the-measurement-of-methemoglobin-The-color-chart-was-prepared-according_\\u003c/a\\u003e\\u003ca href=\\\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536159/figure/f2/\\\" target=\\\"figure\\\"\\u003efig2\\u003c/a\\u003e_26884296\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"6.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7106284/v1/006df35edc2cd714d8f46431.jpg\"},{\"id\":86772603,\"identity\":\"e5ed0dc1-46ab-4683-ba20-bc925816ab4c\",\"added_by\":\"auto\",\"created_at\":\"2025-07-15 12:07:04\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":1862217,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7106284/v1/e5833617-34cb-4735-921b-533dd93bdd3e.pdf\"},{\"id\":86769640,\"identity\":\"b3d28b2a-a954-4493-8b41-16279ebbb9a6\",\"added_by\":\"auto\",\"created_at\":\"2025-07-15 11:35:04\",\"extension\":\"pptx\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":1463661,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"jonnycasepresentationfigures.pptx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7106284/v1/5377e1c78161782e7b99794e.pptx\"}],\"financialInterests\":\"The authors declare no competing interests.\",\"formattedTitle\":\"\\u003cp\\u003eA Catastrophic complication of Methemoglobinemia induced Status Epilepticus due to Pica for Printing Inks and Dyes: A Case Report\\u003c/p\\u003e\",\"fulltext\":[{\"header\":\"BACKGROUND\",\"content\":\"\\u003cp\\u003ePrinting industry execute various printing operations such as letterpress, lithography, flexography, gravure, and screen printing. Nitrobenzene is a major chemical intermediate in the production of printing dyes and is produced by nitration of benzene. It is considered to be extremely toxic, due to its ability to induce methemoglobinemia and its exposure in humans may occur either by inhalation or through skin, mostly as an occupational hazard.\\u003csup\\u003e\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e\\u003c/sup\\u003e In adults, estimated lethal dose of nitro-benzene ranges from 2 to 6 g and doses less than 0.8 mg/kg/day does not usually cause methemoglobinemia.\\u003csup\\u003e\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e\\u003c/sup\\u003e It is an aromatic nitro-compound, exist as a pale oily liquid with smell similar to bitter almonds. It is readily soluble in organic solvents (alcohol, ether and benzene), highly soluble in lipids but only slightly soluble in water. It is also used in the formation of aniline, benzidine, quinoline, azobenzene, rubber chemicals, drugs and as a solvent in shoe, metal polishes and in screen-printing. A major part of the exposed dose is excreted through urine. Concentration of 4-nitrophenol may be used for biological monitoring, since this compound constitutes 10–20% of the excreted dose whereas 4- aminophenol is excreted as a smaller fraction.\\u003csup\\u003e\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e\\u003c/sup\\u003e Acute poisoning with nitrobenzene presenting with methemoglobinemia is a rare medical emergency. This case report narrates an unusual case of acute nitrobenzene poisoning due to an intentional inhalation attempt for strange craving of printing inks and dyes by a young boy.\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\"},{\"header\":\"CASE DESCRIPTION\",\"content\":\"\\u003cp\\u003e\\u003cb\\u003ePresenting Complaints\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eA 17-year young male was apparently well before he had two episodes of vomiting which were acute in onset, intermittent, non-projectile, non-bilious, and non-bloody. After an interval of ten minutes, patient had another episode of vomiting followed by unconsciousness associated with frothing from mouth, clenching of teeth and generalized abnormal body movements.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eInitial Management at Local hospital\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003ePatient was taken to a nearby hospital by family members, where local practitioner suspected it as a case of poisoning and started initial management accordingly. All of the sudden, patient became completely unresponsive with non-palpable carotid pulse (cardiac -arrest). Immediately cardio-pulmonary resuscitation was started and continued till the patient achieved return of spontaneous circulation. After patient was revived, he was shifted to our tertiary care centre.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eAssessment and Management at Emergency department of tertiary care hospital\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eAt the time of arrival in emergency, patient was cyanosed (central as well as peripheral), Glasgow coma score was 3/15 (E1V1M1), SPO2 was 56%, heart rate was 111 beats/min and respiratory rate was 20 breaths/ min. Emergency physician immediately intubated the patient and planned to shift the patient to Intensive care unit for further management. All of the sudden, patient manifested one episode of generalized tonic-clonic seizure in the emergency ward itself, for which patient was given injection levipill 1 gram stat and then shifted to ICU. While being transported to the ICU from emergency ward, patient heart rate dropped (bradycardia) and Injection Atropine 0.5mg was given on the way.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eAssessment and Management at Intensive Care Unit (\\u003c/b\\u003eTable\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e\\u003cb\\u003e)\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e\\u003ccaption language=\\\"En\\\"\\u003e\\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e\\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\u003cp\\u003eSerial monitoring of physiological \\u0026amp; hemodynamic parameters and management done for the patient at ICU from day1 to day 5\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/caption\\u003e\\u003ccolgroup cols=\\\"6\\\"\\u003e\\u003c/colgroup\\u003e\\u003cthead\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eDay 1\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eDay 2\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eDay 3\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eDay 4\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003eDay 5\\u003c/p\\u003e\\u003c/th\\u003e\\u003c/tr\\u003e\\u003c/thead\\u003e\\u003ctbody\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eGCS score\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eE1V1M1 (3/15)\\u003c/p\\u003e\\u003cp\\u003eAnd then patient was intubated, hence E1VTM1\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eE1V1M1 (3/15)\\u003c/p\\u003e\\u003cp\\u003eUnder sedation\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eE4VTM6\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eE4VTM6\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003eE4V5M6\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colspan=\\\"6\\\" nameend=\\\"c6\\\" namest=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eVitals\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eSPO2-56% on O2 mask\\u003c/p\\u003e\\u003cp\\u003eHR- 111/ min\\u003c/p\\u003e\\u003cp\\u003eRR-20/min\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eAfter intubation\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eSPO2 by pulse oximetry: 80%\\u003c/p\\u003e\\u003cp\\u003eSPO2 by Cooximetry-96% with a saturation gap of 16%.\\u003c/p\\u003e\\u003cp\\u003eBP: 80/40 mm of Hg\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eSPO2: 93%\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eSPO2: 93%\\u003c/p\\u003e\\u003cp\\u003eBP:120/80 mm of Hg\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eSPO2: 96%\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003eSPO2: 95%\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colspan=\\\"6\\\" nameend=\\\"c6\\\" namest=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eVentilatory settings\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eMode\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eVolume control\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eVC\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eVC\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eVC\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\" morerows=\\\"4\\\" rowspan=\\\"5\\\"\\u003e\\u003cp\\u003eExtubated\\u003c/p\\u003e\\u003cp\\u003eOn O2 mask @6L/ minute\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eFiO2\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e100%\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e100%\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e60%\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e50%\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eRespiratory rate\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e15/ min\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e15/ min\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e15/ min\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e15/ min\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003ePEEP\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e7 cm of H2O\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e5\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e5\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e5\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eTidal volume\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e380ml\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e380 ml\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e380 ml\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e380 ml\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colspan=\\\"6\\\" nameend=\\\"c6\\\" namest=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eFindings of Urine\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eColour of urine\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eGreen\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eGreen\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eGreen\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eGreen\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eUrinary output\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e100ml/hr\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eMeth haemoglobin levels\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e42.8%\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eMorning-25%\\u003c/p\\u003e\\u003cp\\u003eEvening-42%\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eMorning-19%\\u003c/p\\u003e\\u003cp\\u003eEvening-0.3%\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.1%\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e6%\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colspan=\\\"6\\\" nameend=\\\"c6\\\" namest=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eEchocardiography\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eEF 40%\\u003c/p\\u003e\\u003cp\\u003eType 2 diastolic dysfunction of left ventricle\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eEF 56%\\u003c/p\\u003e\\u003cp\\u003eNo RWMA\\u003c/p\\u003e\\u003cp\\u003eNormal systolic function\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colspan=\\\"6\\\" nameend=\\\"c6\\\" namest=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eMedications\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e(Injection midazolam 4 mg Injection Propofol 100mg Injection Phenytoin 100mg Injection Thiamine 100 mg)-stat\\u003c/p\\u003e\\u003cp\\u003eInjection Midazolam @ 15mg/hour\\u003c/p\\u003e\\u003cp\\u003eInjection Propofol @ 50 mg/ hour.\\u003c/p\\u003e\\u003cp\\u003eInjection Nor-adrenaline @ 10ml/hr\\u003c/p\\u003e\\u003cp\\u003eInjection Vasopressin @4.5ml/hr was started.\\u003c/p\\u003e\\u003cp\\u003eInjection methylene blue 60 mg\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eInjection Midazolam @ 15mg/hour\\u003c/p\\u003e\\u003cp\\u003eInjection\\u003c/p\\u003e\\u003cp\\u003eInjection Nor-adrenaline @ 5ml/hr\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eInjection Nor-adrenaline @ 2ml/hr\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003eInjection dex-medetomidine @3/hr\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tbody\\u003e\\u003c/table\\u003e\\u003c/div\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003cp\\u003eInitial assessment at ICU was done by the intensivist with an approach of ABCDE (Airway, Breathing, Circulation, Disability, Exposure). Patient was having endotracheal tube in-situ and SPO2 was 60% on bains circuit, chest was bilaterally clear, heart rate was 100 beats /minute, pupils were bilaterally reactive to light. Patient was put on ventilator with the settings of volume control (VC) mode, FiO2-100%, tidal volume- 380 ml, respiratory rate-15 breaths/minute, Positive end expiratory pressure (PEEP)-7/minute. Patient again had episodes of generalized tonic-clonic seizures, for which patient was given stat medications ( Injection midazolam 4 mg, propofol 100mg, phenytoin 100mg and thiamine 100 mg) and then infusion of midazolam was started at the rate of 15mg/hour and propofol infusion was started at the rate of 50 mg/ hour. With this management, abnormal body movements decreased and finally stopped. Central intra-venous access was established through central venous pressure line. Invasive blood pressure monitoring revealed the reading of 80/40 mm of Hg for which infusion of injection nor-adrenaline at the rate of 10ml/hr and vasopressin at the rate of 4.5ml/hr was started.\\u003c/p\\u003e\\u003cp\\u003eAfter establishing the haemodynamic stability of the patient, thorough history was obtained from the patient’s family members (parents) which revealed that, patient’s father has printing press business and the patient likes the smell of printed materials (inks and dyes). With this information, intensivist suspected the occupational exposure of nitrous compounds. By keeping this suspicion in mind, patient’s blood sample was withdrawn for arterial blood gases (ABG) and other investigations and it was observed that the colour of the blood was dark brown. ABG report demonstrated metabolic acidosis (pH- 7.2, PCO2- 34.7 mm of Hg, HCO3-14.6, Lactate-7.38 and BE-11.7). Amount of met-haemoglobin was also assessed in ABG and found to be 42.8% (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). SPO2 by pulse oximetry was 80% and by co-oximetry was 96% and there was a saturation gap of 16%. Patient’s ECG depicted global T wave inversion and echocardiography demonstrated ejection fraction of 40% and type 2 diastolic dysfunction of left ventricle. Patient was started on methylene blue (60 mg) as per the dose of 1mg/Kg. Urinary catheter was inserted and it was observed that colour of the urine turned to green (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e5\\u003c/span\\u003e) after administration of methylene blue, which is an antidote for methemoglobinemia by conversion of ferric (Fe\\u003csup\\u003e3+\\u003c/sup\\u003e) state of iron to ferrous (Fe\\u003csup\\u003e2+\\u003c/sup\\u003e) form and therefore leads to reversal of MeHb back to Hb.\\u003c/p\\u003e\\u003cp\\u003eSerial monitoring of patient’s acid-base status was continued. A decrease in the percentage of methaemoglobin, vital signs and hemodynamic parameters normalization and adequate response to the provided management was observed (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e,\\u003cspan refid=\\\"Fig5\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e). Patient had no signs of infection, no increase in inflammatory parameters, so there was no indication for antibiotics. The patient recovered fully within few days and was discharged from the hospital in a satisfactory condition. At the time of discharge, verbal informed consent was obtained from the patient and parents \\u0026amp; they gave their approval for the documentation of this case along with relevant findings.\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eNitrobenzene ingestion (inhalation or topical absorption) oxidises iron in haemoglobin (Hb) to form methaemoglobin. Methemoglobinemia is an unusual clinical condition characterized by the alteration of divalent iron to trivalent form (ferrous to ferric) due to oxidation in the Hb molecule. Haemoglobin can bind to oxygen only in its divalent (ferrous) form, and the allosteric change in Hb molecule as trivalent (ferric) state is no longer be able to bind oxygen. Hence, the physiological alterations and clinical manifestations of methemoglobinemia are a direct consequence of inadequate oxygen transport due to shifting of oxygen\\u0026ndash;haemoglobin dissociation curve to the left, reduced peripheral oxygen release\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e\\u003c/sup\\u003e, hypoxia and functional anemia\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e\\u003c/sup\\u003e with no decrease in Hb level.\\u003c/p\\u003e\\n\\u003cp\\u003eLevel of methaemoglobin (MeHb) in blood is approximately 1% and methemoglobinemia occurs if the level of MeHb goes above this. Low level of MeHb in blood is maintained by two important mechanisms.\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e\\u003c/sup\\u003e First mechanism is the hexose monophosphate shunt pathway within the RBC by which, glutathione reduces oxidising agents before they lead to the formation of MeHb and the second mechanism against MeHb formation comprises of two enzymes systems: diaphorase I (nicotinamide adenine dinucleotide (NADH) methaemoglobin reductase) and diaphorase II (nicotinamide adenine dinucleotide phosphate (NADPH) methaemoglobin reductase). These two enzyme systems require NADH and NADPH, respectively to reduce MeHb back to its original ferrous state.\\u003c/p\\u003e\\n\\u003cp\\u003eIn healthy individuals, level of MeHb must be greater than 10% to be clinically symptomatic and levels of 20\\u0026ndash;30% lead to mild symptoms of headache, fatigue and nausea. Patients represent with dyspnoea on exertion (DOE), lethargy and tachycardia with the levels of 30\\u0026ndash;45%. Life threatening manifestations of arrhythmias, coma, seizures, respiratory distress and lactate acidosis occurs with the levels of 45\\u0026ndash;70%. Levels greater than 70% are fatal due to cardiovascular collapse and is associated with high degree of mortality if left untreated.\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e\\u003c/sup\\u003e Most important manifestations\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e\\u003c/sup\\u003e in suspecting the diagnosis of met-hemoglobinemia are: \\u003cstrong\\u003eDark or chocolate brown colour of blood\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/sup\\u003e. Both MeHb and deoxygenation causes change in blood colour from red to brown. Difference in both the conditions is that in case of MeHb, after putting blood on white gauge, the blood will remain brown after getting dry also, whereas in deoxygenated blood, it will turn red again after absorbing environmental O2, \\u003cstrong\\u003erefractory hypoxia, central cyanosis with saturation gap\\u003c/strong\\u003e: Appearance of cyanosis with SPO2 of 80\\u0026ndash;90%. (cyanosis is an uncommon finding at this saturation level). Young boy in this case report presented with vomiting and abnormal body movements followed by cardiac arrest. After achieving return of spontaneous circulation secondary to cardio-pulmonary respiration, patient manifested with repeated episodes of seizures (status epilepticus), arrythmias (bradycardia).\\u003c/p\\u003e\\n\\u003cp\\u003eConfirmation of presence of MeHb in blood is done by additional findings of co-oximetry in ABG analysis. Co-oximetry has the potential to diagnose disorders of methemoglobinemia and carboxy-hemoglobinemia due to its ability of light absorption of various wavelengths: 600nm (carboxyhaemoglobin), 631nm (methaemoglobin), 660nm (deoxyhaemoglobin), and 940 nm.\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e\\u003c/sup\\u003e It is an advantageous and practical tool to monitor amount of MeHb and therefore helps in identification of methemoglobinemia. Additionally, it is helpful for computation of \\u0026ldquo;saturation gap\\u0026rdquo; which is another characteristic of methemoglobinemia, by finding out the difference between oxygen saturation value of blood through pulse-oximeter and co-oximetry. A difference of more than 5% may raise a suspicion of methemoglobinemia. In the present case, patient was cyanosed, hypoxemic with SPO2 of 56% and co-oximetry revealed 42.8% of met-haemoglobin in blood with a saturation gap of 16%. Moreover, when the patient\\u0026rsquo;s blood sample was with-drawn for various investigations and ABG, it was noticed that colour of the blood was dark brown.\\u003c/p\\u003e\\n\\u003cp\\u003eMedical condition of methemoglobinemia may occur as a consequence of either a congenital defect (Table\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e) or as an acquired disorder, however the later cause is more common. Acquired methemoglobinemia may occur as an adverse effect of a drug or exposure to toxins (Table\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e).\\u003c/p\\u003e\\n\\u003cdiv class=\\\"gridtable\\\"\\u003e\\n\\u003cdiv class=\\\"colspec\\\" align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/div\\u003e\\n\\u003ctable id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e\\u003ccaption\\u003e\\n\\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e\\n\\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\n\\u003cp\\u003eList of congenital causes responsible for the development of methemoglobinemia\\u003c/p\\u003e\\n\\u003c/div\\u003e\\n\\u003c/caption\\u003e\\n\\u003cthead\\u003e\\n\\u003ctr\\u003e\\n\\u003cth align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eAffected genes\\u003c/p\\u003e\\n\\u003c/th\\u003e\\n\\u003cth colspan=\\\"2\\\" align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePhysiological alterations\\u003c/p\\u003e\\n\\u003c/th\\u003e\\n\\u003c/tr\\u003e\\n\\u003c/thead\\u003e\\n\\u003ctbody\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eVariants (approximately 80) of the CYB5R3 gene (autosomal recessive mutation)\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eMutation in CYB5R3 gene, leads to NADH-cytochrome-reductase deficiency.\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis enzyme is required to reduce MeHb back to its original ferrous state (Fe\\u003csup\\u003e2+\\u003c/sup\\u003e) from the oxidized ferric form (Fe3\\u003csup\\u003e+\\u003c/sup\\u003e).\\u003c/p\\u003e\\n\\u003cp\\u003eCYB5R3 gene mutation may cause congenital methemoglobinemia type I or type II\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCongenital methemoglobinemia type I\\u003c/strong\\u003e:\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026bull; Reduced activity of this enzyme leads to 10 to 50% of accumulation in MeHb within RBCs in comparison to less than 1% in normal individuals. Decreased activity of enzyme affects only erythrocytes because RBCs are unable to compensate the deficiency whereas other cells can withstand these reduced levels.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026bull; Neonates with type-I congenital methemoglobinemia manifest with cyanosis since birth and develop shortness of breath in response to decreased level of oxygen.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026bull; These children have normal life expectancy.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCongenital methemoglobinemia type II\\u003c/strong\\u003e:\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026bull; Complete loss of this enzyme leads to marked increase in MeHb levels (upto 70%).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026bull; These patients present with cyanosis as well as severe neurological problems. These children may develop following conditions: -\\u003c/p\\u003e\\n\\u003cp\\u003e❖ Severe brain dysfunction (Encephalopathy)\\u003c/p\\u003e\\n\\u003cp\\u003e❖ Tensed muscles (Dystonia)\\u003c/p\\u003e\\n\\u003cp\\u003e❖ Involuntary limb movements (choreoathetosis)\\u003c/p\\u003e\\n\\u003cp\\u003e❖ Microcephaly\\u003c/p\\u003e\\n\\u003cp\\u003e❖ Severe intellectual disability\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026bull; These children often do not survive past early adulthood.\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eMutations in various genes encoding globin protein (autosomal dominant disease)\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eThese mutations can cause structural abnormalities in alpha, beta and gamma-globin.\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eStructural abnormalities in globin chains of Hb may lead to auto-oxidation of iron, and therefore to the development of methemoglobinemia.\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003c/div\\u003e\\n\\u003cdiv class=\\\"gridtable\\\"\\u003e\\n\\u003cdiv class=\\\"colspec\\\" align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/div\\u003e\\n\\u003cdiv class=\\\"colspec\\\" align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/div\\u003e\\n\\u003ctable id=\\\"Tab3\\\" border=\\\"1\\\"\\u003e\\u003ccaption\\u003e\\n\\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 3\\u003c/div\\u003e\\n\\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\n\\u003cp\\u003eList of acquired causes responsible for the development of methemoglobinemia\\u003c/p\\u003e\\n\\u003c/div\\u003e\\n\\u003c/caption\\u003e\\n\\u003cthead\\u003e\\n\\u003ctr\\u003e\\n\\u003cth align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eDrugs\\u0026rsquo; or Agents\\u0026rsquo; Category\\u003c/p\\u003e\\n\\u003c/th\\u003e\\n\\u003cth align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eList of drugs or agents under the category\\u003c/p\\u003e\\n\\u003c/th\\u003e\\n\\u003c/tr\\u003e\\n\\u003c/thead\\u003e\\n\\u003ctbody\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eNitrates\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e❖ Nitro-glycerin\\u003c/p\\u003e\\n\\u003cp\\u003e❖ Inhaled nitric oxide (Nitro-benzene)\\u003c/p\\u003e\\n\\u003cp\\u003e❖ Nitroprusside\\u003c/p\\u003e\\n\\u003cp\\u003e❖ Oral nitrates\\u003c/p\\u003e\\n\\u003cp\\u003e❖ Amyl-nitrate\\u003c/p\\u003e\\n\\u003cp\\u003e❖ Contaminated water or vegetable broths with high nitrate levels: Mostly infants are affected due to consumption of powdered formula or soups with high levels of nitrates (most commonly carrots and spinach)\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eLocal\\u003c/p\\u003e\\n\\u003cp\\u003eAnaesthetic drugs\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e❖ Lidocaine\\u003c/p\\u003e\\n\\u003cp\\u003e❖ Benzocaine\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eOncological drugs (alkylating agents)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e❖ Cyclophosphamide\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eAntiemetics\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e❖ Metoclopramide\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eAntibiotics\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e❖ Dapsone\\u003c/p\\u003e\\n\\u003cp\\u003e❖ Rifampicin\\u003c/p\\u003e\\n\\u003cp\\u003e❖ Sulfonamides\\u003c/p\\u003e\\n\\u003cp\\u003e❖ Antimalarials\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eEnzyme used to lower down uric acid levels\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e❖ Rasburicase (More frequent cause in patients with G6PD deficiency)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003c/div\\u003e\\n\\u003cp\\u003eTreatment of acquired (toxic) methemoglobinemia includes supportive care, symptomatic management and discontinuation of the offending agent or substance. Definitive treatment involves the transformation of methaemoglobin to a non-oxidized state using methylene blue, which is the antidote of choice. Methylene blue acts as an exogenous co-factor, which enhances the NADPH dependent methaemoglobin reductase system.\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e\\u003c/sup\\u003e It acts by accepting an electron from NADPH and therefore reduces trivalent iron (ferric form) of MeHb to ferrous form (Haemoglobin) and indicated for patients who are symptomatic or whose co-oximetry represents MeHb level more than 30%The initial dose is 1 to 2 mg/kg or 0.1 to 0.2 ml/kg of the 3% solution given intravenously over 5 min. Clinical response is evident within few minutes of methylene blue administration and cyanosis usually resolves in one hour. After administration of methylene blue, SPO2 values drop via pulse-oximetry due to bluish discolouration of blood. If the cyanosis persist after 60 minutes of administration, then drug dose can be repeated with an escalated dose up-to 2mg/kg and in case, patient does not respond in terms of cyanosis at this dose also, then glucose-6-phosphate dehydrogenase (G6PD) deficiency should be considered. Rebound-methemoglobinemia may recur within 12 hours of drug administration, for which methylene blue may be administered through continuous infusion. Dose calculation as per the body weight carries utmost importance, since in higher doses \\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e\\u003c/sup\\u003e, methylene blue itself acts as an oxidising agent and asymptomatic methemoglobinemia occur with a dose of 5mg/kg.\\u003csup\\u003e15\\u003c/sup\\u003eCumulative doses greater than 7 mg/kg accelerates risk of methaemoglobin induction. Definitive management of patient in the present case report was attempted by the administration of methylene blue with a dose of 1ml/kg. Patient responded well, with a de-escalation of MeHb levels from 48\\u0026ndash;25%. This patient also showed rebound methemoglobinemia with rise in MeHb levels from 25\\u0026ndash;42% ( Table\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e\\n\\u003cp\\u003eG6PD deficiency is a relative contraindication for consideration of methylene blue as an antidote to MeHb, because these patients lack NADPH and hence, methylene blue is either completely ineffective or has only little effect. Moreover, methylene blue decreases the level of glutathione due to existing low NADPH, which subsequentially leads to breakdown of erythrocytes (haemolysis).\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e\\u003c/sup\\u003e Patients with G6PD deficiency are the candidates for treatment with high doses of vitamin C (1.5-3g IV every six hours) along with riboflavin (vitamin B2), which is an electron acceptor. In case of refractory methemoglobinemia to all of the above mentioned treatment alternatives, complete erythrocyte transfusion and hyperbaric chamber transplantation may be an option to be contemplated. Young boy in the current case scenario responded well to methylene blue with a dose of 1mg/kg and therefore indication for the administration of vitamin C and riboflavin was not considered.\\u003c/p\\u003e\\n\\u003cp\\u003eMethylene blue is a monoamine oxidase (MAO) inhibitor and may induce serotonin syndrome. Other side effects are systemic and/or pulmonary hypertension (via a reaction that fails nitric oxide-mediated vasodilation), motor restlessness, dyspnea, nausea, vomiting, sweating, and anaphylactic reaction\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e\"},{\"header\":\"Conclusion\",\"content\":\"\\u003cp\\u003eNitrobenzene ingestion results in severe oxidative stress as exhibited by increased levels of methaemoglobin which leads to the clinical condition of methemoglobinemia. This disorder is characterized by oxidation of iron inside the Hb molecule which makes it unable to bind with oxygen. Acquired (Toxic) methemoglobinemia is an acute condition that develops as a consequence of either the side effect of certain drugs or poisoning with nitrate compounds. Magnitude and severity of symptoms depends on the MeHb percentage in the blood, and clinical presentation has a vast array that may vary from vomiting, fatigue, anxiety, dizziness, and cyanosis, to life threatening complications decreased level of consciousness, epileptic seizures, arrhythmia and coma. Differential diagnosis of methemoglobinemia crosses the treating physician’s mind with the manifestations of refractory hypoxia, cyanosis-saturation gap and dark brown blood Definitive diagnosis is made using co-oximetry by detecting MeHb levels along with saturation gap. Management focuses on emergency management of arrythmias, seizures, hypoxia etc. along with administration of oral or parenteral administration of methylene blue (antidote of choice).\\u003c/p\\u003e\"},{\"header\":\"Clinical Significance\",\"content\":\"\\u003cp\\u003eRebound-methemoglobinemia may recur within 12 hours of drug administration, for which methylene blue may be administered through continuous infusion. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a relative contraindication for consideration of methylene blue as an antidote to MeHb, and these patients needs to be treated with high doses of vitamin C along with vitamin B2. In case of refractory methemoglobinemia, to all of the mentioned treatment alternatives, complete erythrocyte transfusion and hyperbaric chamber transplantation may be an option to be contemplated\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eWright RO, Lewander WJ, Woolf AD (1999. November) Methemoglobinemia: etiology, pharmacology, and clinical management. 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Available from: \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://www.cdc.gov/mmwr/preview/mmwrhtml/mm 6105a1.htm?s_cid\\u0026thinsp;=\\u0026thinsp;mm6105a1_w\\u003c/span\\u003e\\u003cspan address=\\\"https://www.cdc.gov/mmwr/preview/mmwrhtml/mm 6105a1.htm?s_cid\\u0026thinsp;=\\u0026thinsp;mm6105a1_w\\\" targettype=\\\"URL\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e [PubMed] [Ref list]\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eWhitwan JG, Taylor AR, White JM Potential hazard of methylene blue. Anaesthesia 1979 ; 34 : 181\\u0026ndash;2\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eRehman A, Shehadeh M, Khirfan D, Jones A (2018) Severe acute haemolytic anaemia associated with severe methaemoglobinaemia in a G6PD-deficient man. BMJ Case Rep. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1136/bcr-2017-223369\\u003c/span\\u003e\\u003cspan address=\\\"10.1136/bcr-2017-223369\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e[PMC free article] [PubMed] [CrossRef] [Google Scholar] [Ref list] \\u0026bull;\\u0026bull;\\u0026bull;:bcr-2017-223369\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eIvek I, Knotek T, Ivičić T, Rubinić B, Bajlo P, Hamzić J (2022) METHEMOGLOBINEMIA - A CASE REPORT AND LITERATURE REVIEW. Acta Clin Croatica 61(Suppl 1):93\\u0026ndash;98. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.20471/acc.2022.61.s1.16\\u003c/span\\u003e\\u003cspan address=\\\"10.20471/acc.2022.61.s1.16\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":true,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Methemoglobinemia, Nitrobenzene, printing inks/dyes\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-7106284/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-7106284/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eAim \\u0026amp; Background\\u003c/strong\\u003e: Nitrobenzene ingestion is extremely toxic \\u0026amp; leads to the clinical condition of methemoglobinemia. This disorder is characterized by severe oxidation of iron inside the Hb molecule and that makes it unable to bind with oxygen. Clinical presentation depends on the methaemoglobin (MeHb) levels in blood. This case report narrates an unusual case of acute nitrobenzene poisoning due to an intentional inhalation attempt to satisfy the strange craving for printing inks and dyes by a young boy.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCase description\\u003c/strong\\u003e: Patient presented with symptoms of poisoning (vomiting, seizures) and subsequently landed into cardiac arrest. After revival, patient continued presenting with repeated episodes of seizures \\u0026amp; bradycardia. Patient was medically managed by cardio-pulmonary resuscitation followed by endotracheal intubation along with pharmacological management of atropine, levipill, propofol, phenytoin, midazolam, thiamine \\u0026amp; methylene blue (antidote of choice).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusion\\u003c/strong\\u003e: Exposure of nitrobenzene may occur either by inhalation or through skin, mostly as an occupational hazard. Differential diagnosis of methemoglobinemia crosses the treating physician’s mind with the manifestations of refractory hypoxia, cyanosis-saturation gap and dark brown blood. Definitive diagnosis is made using co-oximetry by detecting MeHb levels along with saturation gap. Treatment of acquired methemoglobinemia includes supportive care, symptomatic management and discontinuation of the offending agent. Definitive treatment involves the transformation of methaemoglobin to a non-oxidized state using methylene blue.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eClinical significance\\u003c/strong\\u003e: Rebound-methemoglobinemia may recur within 12 hours of drug administration, for which methylene blue may be administered through continuous infusion. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a relative contraindication for consideration of methylene blue as an antidote to MeHb, and these patients needs to be treated with high doses of vitamin C along with vitamin B2. In case of refractory methemoglobinemia, to all of the mentioned treatment alternatives, complete erythrocyte transfusion and hyperbaric chamber transplantation may be an option to be contemplated.\\u003c/p\\u003e\",\"manuscriptTitle\":\"A Catastrophic complication of Methemoglobinemia induced Status Epilepticus due to Pica for Printing Inks and Dyes: A Case Report\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-07-15 11:34:59\",\"doi\":\"10.21203/rs.3.rs-7106284/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"af305f4a-de1c-4f72-8e1e-43adcc8acb98\",\"owner\":[],\"postedDate\":\"July 15th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[{\"id\":51539351,\"name\":\"Critical Care \\u0026 Emergency Medicine\"}],\"tags\":[],\"updatedAt\":\"2025-07-15T11:34:59+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-07-15 11:34:59\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-7106284\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-7106284\",\"identity\":\"rs-7106284\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}