|Year : 2014 | Volume
| Issue : 2 | Page : 185-187
Nitrobenzene poisoning presenting as Methemoglobinemia
Amit A Bharadiya1, Akshay N Lakhotia1, Aparna Patange1, Jyotsna B Jaju2, Kushal Choraria1
1 Department of Medicine, Krishna Institute of Medical Sciences and Research Centre, Karad, India
2 Department of Biochemistry, Swami Ramanand Teerth Government Medical College, Ambajogai, Maharashtra, India
|Date of Web Publication||1-Jul-2014|
Amit A Bharadiya
Room No. 102, I.H.R Hostel, Krishna Institute of Medical Sciences, Karad - 415 110, Maharashtra
Source of Support: None, Conflict of Interest: None
Consumption of toxic compounds in an attempt to commit suicide is very common. Organophosphorus compounds are the most commonly consumed and fatal poisons. Nitrobenzene consumption for suicidal purposes is very rare. We would like to report a case of acute poisoning with nitrobenzene leading to methemoglobinemia, an unusual presentation.
Keywords: Methemoglobinemia, nitrobenzene, poisoning
|How to cite this article:|
Bharadiya AA, Lakhotia AN, Patange A, Jaju JB, Choraria K. Nitrobenzene poisoning presenting as Methemoglobinemia. Muller J Med Sci Res 2014;5:185-7
|How to cite this URL:|
Bharadiya AA, Lakhotia AN, Patange A, Jaju JB, Choraria K. Nitrobenzene poisoning presenting as Methemoglobinemia. Muller J Med Sci Res [serial online] 2014 [cited 2020 Aug 10];5:185-7. Available from: http://www.mjmsr.net/text.asp?2014/5/2/185/135774
| Introduction|| |
Nitrobenzene, an aromatic nitro compound, occurs as a pale yellow moderately water-soluble oily liquid with an odor resembling that of bitter almonds. It is slightly soluble in water; readily soluble in organic solvents such as alcohol, ether, and benzene; and highly soluble in lipids. It is used in the manufacture of aniline, benzidine, quinoline, azobenzene, rubber chemicals, drugs, and dyes; as a solvent in shoe and metal polishes; and in screen-printing. Its toxic effects are due to its ability to induce methemoglobinemia,  which is difficult to diagnose clinically and not routinely suspected. Our case had this rare presentation.
| Case Report|| |
A 17-years-old unmarried female was admitted to our hospital's critical care unit with the alleged history of consumption of unknown compound after a quarrel in the family around an hour ago. Patient complained of epigastric discomfort and nausea. She did not have any vomiting, loss of consciousness, or seizures while being transferred to the hospital.
On general examination, she was conscious, had a pulse of 110/min, BP read 110/70 mmHg, and room air oxygen saturation was 94%. Her pupils were normal and reacting to light. There was no pallor, icterus, cyanosis, lymphadenopathy, head lag, respiratory distress, pungent odor of the organophosphorus compounds, flaps, or altered mental status. Her systemic examination was also unremarkable except for the sinus tachycardia. She was given thorough gastric lavage and supportive care was started.
After 2 hours, she developed central cyanosis and her room air oxygen saturation dropped to 64% which was not improving with noninvasive ventilation also. Her cardiorespiratory examination was normal. Blood samples drawn for arterial blood gas (ABG) had a chocolate brown color, which did not improve on exposure to 100% oxygen and showed compensated metabolic acidosis [Table 1].
Investigation showed serum cholinesterase levels of 12760 IU/L and random blood sugar of 96 mg/dl, serum electrolytes were sodium (Na) 141 mg/dl, potassium (K) 4.5 mg/dl, calcium (Ca) 8.6 mg/dl. Kidney and liver function were normal. Complete blood count, urine routine examinations were within normal limits. Chest radiograph and electrocardiogram was normal. 2D-echocardiogram done showed no significant cardiac abnormality. Arterial blood gas analysis could not be done. Methemoglobinemia was suspected as it shows similar presentation and serum methemoglobin (MeHb) estimation was done. Its value was significantly raised. It was 30% on day 1. She was given injectable methylene blue at a dose of 1 mg/kg intravenously slowly over 5 minutes. Tablet Vitamin C 500 mg 6 hourly was also given. Meanwhile, as we were searching for the cause for her methemoglobinemia, we strongly suspected it to be the unknown compound which she had consumed. On asking the patients' relatives to bring the compound container from their house, we find out that it was nitrobenzene. Her serum MeHb levels repeated on day 3 was 10% only. Cyanosis had resolved and room air oxygen saturation had returned to normal. Patient was discharged on the 4 th day and advised to come for follow-up after a week.
| Discussion|| |
Nitrobenzene is an oxidizing nitrite compound. Nitrobenzene ingestion oxidizes iron in hemoglobin to form MeHb Acute ingestion of nitrobenzene leads to rapid development of methemoglobinemia.  The low level of MeHb is maintained by two important mechanisms.  One is the hexose monophosphate shunt pathway within the erythrocyte by which oxidizing agents are reduced by glutathione prior to the formation of MeHb. The second mechanism against MeHb formation uses two enzymes systems: Diaphorase I (nicotinamide adenine dinucleotide, NADH, MeHb reductase) and diaphorase II (nicotinamide adenine dinucleotide phosphate, NADPH, MeHb reductase). These two enzyme systems require NADH and NADPH, respectively to reduce MeHb to its original ferrous state. Diaphorase II quantitatively contributes only a small percentage of the reducing capacity of red blood cells (RBC). MeHb is normally less than 1% of the total hemoglobin under physiologic conditions. When its levels increase, the condition is defined as methemoglobinemia. The estimated lethal dose ranges from 2 gm to 6 gm in adults; and doses less than 0.8 mg/kg/day does not normally cause methemoglobinemia.  Methemoglobinemia can be acquired secondary to exposure to oxidant agents; few such agents commonly used in anesthesia practice include nitroglycerine, local anesthetics like lidocaine and prilocaine. , Congenital causes of methemoglobinemia include deficiency of enzyme NADH cytochrome-b5 reductase (autosomal recessive), cytochrome-b5 deficiency (autosomal recessive), or hemoglobin M disease due to globin chain mutation (autosomal dominant). , In normal individuals, MeHb level must be greater than 10% to be clinically significant, and only mild symptoms like headache, fatigue, and nausea occur at a level of 20-30%.  Exertional dyspnea, lethargy, and tachycardia occur at levels of 30-45%. Arrhythmias, coma, seizures, respiratory distress, and lactate acidosis occur at levels of 50-70%. Levels greater than 70% cause cardiovascular collapse and have a high degree of mortality if left untreated.  In significant nitrobenzene poisoning with methemoglobinemia, arterial blood gas analysis reveals lactate metabolic acidosis, tissue ischemia, and hypoxia. PaO2 remains normal, measured (not calculated) oxygen saturation will be low.  Transcutaneous pulse-oximetry estimation of oxygen saturation is lowered by methemoglobinemia. Spuriously high pulse-oximetry readings are possible with increasing concentrations.  Patients with symptomatic methemoglobinemia require intensive monitoring until symptoms clear or the MeHb level is below 15%.  Pattern recognition is key: Cyanosis, low hemoglobin oxygen saturation on pulse oximetry (typically 85-89%, representing the absorbance spectrum of methemoglobin), normal PaO2 on ABG, "chocolate blood" (Note, methemoglobinemia does not change color with the addition of oxygen, whereas dark blood due to deoxyhemoglobin will turn red with oxygen.). Co-oximetry of ABG will quantify the percentage of methemoglobinemia in a fresh arterial sample. Methylene blue is the antidote of choice for acquired (toxic) methemoglobinemia.  It acts as an exogenous co-factor which greatly accelerates the NADPH-dependent MeHb reductase system.  Methylene blue is indicated for acquired methemoglobinemia when the level is greater than 35-40% and the patient has cardiorespiratory symptoms. , The initial dose is 1-2 mg/kg or 0.1-0.2 ml/kg of the 3% solution given intravenously over 5 minutes.  Response occurs within 1 hour and reduces the elimination half-life of severe methemoglobinemia to 45-90 minutes. MeHb levels should be checked 1 hour after infusion and a repeat dose may be warranted if levels remain high and the patient is still symptomatic. In higher doses, methylene blue itself is an oxidizing agent and as little as 5 mg/kg has caused asymptomatic methemoglobinemia.  Cumulative doses greater than 7 mg/kg have an increased risk of MeHb induction.
If methylene blue is contraindicated or ineffective, ascorbic acid is often mentioned as an alternative therapy, but its reducing effect is probably too slow to have significant benefit.  Exchange transfusion is indicated in severe cases, when both fail. Exchange transfusions equal to or less than the total volume and up to greater than twice the volume have been used.  The present index case represents an uncommon poisoning with nitrobenzene, which was managed successfully with intravenous methylene blue and ascorbic acid with intensive hemodynamic and cardiopulmonary support.
| References|| |
|1.||Schimelman MA, Soler JM, Muller HA. Methaemoglobinem: Nitrobenzene ingestion. JACEP 1978;7:406-8. |
|2.||Patel A, Dewan A, Upadhyay K, Patel S, Patel J. Chemically induced methemoglobinemia from acute nitrobenzene poisoning. Intern J Lab Med 2008;3. |
|3.||Harris JC, Rumack BH, Paterson RG, McGuire BM. Methaemoglobinemia resulting from absorption of nitrates. JAMA 1979;242:2869-71. |
|4.||Pierce JM, Nielsen MS. Acute acquired methemoglobinemia after amyl nitrite poisoning. BMJ 1989;298:1566. |
|5.||Rieder HU, Frei FJ, Zbinden AM, Thomson DA. Pulse oximetry in methemoglobinemia. Failure to detect low oxygen saturation. Anaesthesia 1989;44:326-7. |
|6.||Howard MR, Hamilton PJ. Hematology. 1 st ed. Edinburgh: Churchill Livingstone; 1997. |
|7.||Abdul Rehmankhan FM, Shah SK. Methemoglobinemia. J Postgrad Med Inst 1990;1:174-7. |
|8.||Walley T, Flangan M. Nitrite-induced methaemoglobinemia. Postgrad Med J 1987;63:643-44. |
|9.||Eisenkraft JB. Pulse oximeter desaturation due to methaemoglobinemia. Anaesthesiology 1988;68:s279-82. |
|10.||Curry S. Methaemoglobinemia. Ann Emerg Med 1982;11:214-21. |
|11.||Whitwan JG, Taylor AR, White JM. Potential hazard of methylene blue. Anaesthesia 1979;34:181-2. |