|Year : 2014 | Volume
| Issue : 4 | Page : 486-488
Methaemoglobinemia - Faulty probe or faulty haemoglobin
Kamal Kishore, Anshuman Singh, Sandeep Sahu, Guru Police Patel
Department of Anaesthesiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
|Date of Web Publication||17-Aug-2014|
Dr. Kamal Kishore
Department of Anaesthesiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh - 226 014
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Kishore K, Singh A, Sahu S, Patel GP. Methaemoglobinemia - Faulty probe or faulty haemoglobin. Indian J Anaesth 2014;58:486-8
| Introduction|| |
Pyridium or phenazopyridine hydrochloride is in the pharmacological category of urinary analgesics. It is a commonly prescribed medication for the treatment of urinary tract infections and is known to cause methaemoglobinemia when used in excessive doses. Methaemoglobinemia causes interference with normal oxygen delivery.  Apart from its potential to interfere with oxygen delivery, it can interfere with pulse oximeter readings and some existing medications can cause or exacerbate pre-existing methaemoglobinemia.  These patients should be managed keeping in mind possible causes, removal of the offending agent if possible, using methylene blue if methaemoglobin level is high and ensuring optimal tissue oxygen delivery.
At our institute a 14-year-old patient presented with a history of continuous dribbling of urine per urethra since birth. Patient was scheduled to undergo retrograde pyelography and definitive management. Preanaesthetic evaluation revealed no significant findings except for the history of the patient being on oral pyridium for previous 2 days (200 mg thrice daily). Respiratory system evaluation was normal and X-ray chest was also normal. After shifting the patient to the operation theatre, we attached all the monitors. Non-invasive blood pressure (116/70 mm Hg), and electrocardiogram were normal.Pulse oximetric oxygen saturation was 93% on room air. The SPO 2 probe was attached to other extremity but saturation level remained the same. Patient was preoxygenated with 100% oxygen for 5 min but the oxygen saturation remained at 93-94%. Thinking it as a technical error of the pulse oximeter probe, anaesthesia was induced with midazolam-1.5 mg, fentanyl-125 μgm, thiopentone-200 mg, vecuronium-4 mg and trachea was intubated with cuffed endotracheal tube (6.5 mm). Patient was put on ventilator with 100% oxygen initially but oxygen saturation remained 93-94% even after 10 min.
An arterial line was placed on the right radial artery and an arterial blood gas (ABG) sample was sent for analysis [Table 1]. The ABG failed to estimate haemoglobin in that sample. Samples of other patients being operated on the same day had no problems with haemoglobin estimation thus ruling out any technical error with the ABG machine.
On retrospective analysis, the fact of the patient being on pyridium came up as a possible source of methaemoglobinemia. We sent a blood sample for methaemoglobin estimation which was 1.9% in that sample (normal <1.1%). The co-oximeter was not available in our institute, so it was not used in the diagnosis of methaemoglobinemia of this patient.
The duration of the procedure was 3 hours 45 minutes and the saturation of the patient gradually improved. Patient remained haemodynamically stable throughout the procedure. At the end of the procedure patient was reversed with neostigmine (0.05 mg/kg) and glycopyrolate (8 μgm/kg) and her trachea was extubated after complete neuromuscular recovery. Patient was shifted to post-operative recovery room where she maintained 97% oxygen saturation on room air. She was shifted to the ward 2 h later.
| Discussion|| |
Phenazopyridine is a chemical which, when excreted into the urine, has a local analgesic effect. It is often used to alleviate the pain, irritation, discomfort, or urgency caused by urinary tract infections, or injury. Phenazopyridine can cause a pigment change in the skin or eyes, to a noticeable yellowish colour. 
Phenazopyridine should be avoided by people with glucose-6-phosphate dehydrogenase deficiency , because it can cause haemolysis due to oxidative stress.  It has been reported to cause methaemoglobinemia after overdose and even with normal doses.
Haemoglobin molecules contain iron within a porphyrin haem structure. The iron moieties in haemoglobin are in the ferrous state (Fe 2+ ) in both oxyhaemoglobin and deoxyhaemoglobin and are capable of reversibly binding with oxygen only in this (ferrous) state. The oxidation of iron to the ferric state (Fe 3+ ) results in the formation of methaemoglobin.
An oxidized ferric iron (Fe + 3) is responsible for methemoglobin's inability to bind oxygen. In addition, ferric iron has slightly greater affinity for oxygen, thus shifting the oxygen dissociation curve to the left, resulting in decreased release of oxygen in tissues. The findings of anaemia and cyanosis despite oxygen treatment result from both of these effects. ,
It is important to realize that methaemoglobin is a naturally occuring oxidized metabolite of haemoglobin and physiologic levels (<1%) are normal. Problems arise when levels increase, as methaemoglobin does not bind to oxygen, thus leading to a functional anaemia. ,
In healthy individuals, the ferric iron in methaemoglobin is readily reduced to the ferrous state, primarily through the function of cytochrome b5 oxidase. Cytochrome b5 reductase plays a major role in the reduction of methaemoglobin to haemoglobin. The major enzymatic system involved is adenine dinucleotide (NADH)-dependent methaemoglobin reduction. Another enzyme system, nicotinamide adenine dinucleotide phosphate (NADPH)-dependent methaemoglobin reduction, usually plays only a minor role in the removal of methaemoglobin. Methylene blue accelerates the NADPH-dependent methaemoglobin reduction pathway. ,
The physical examination of patients suspected of methaemoglobinemia should include examination of the skin and mucous membranes for discoloration or cyanosis. Vital signs should be documented.
Careful attention should be paid to the cardiac, respiratory and circulatory examinations to assess for evidence of an underlying disease. Pallor of the skin or conjunctiva may suggest anaemia (and possible haemolysis).
The limitation of ABG is that methaemoglobin can falsely elevate the calculated oxygen saturation. Presence of 'saturation gap' could be a possible clue for the diagnosis of methaemoglobinemia. Saturation gap is the difference in oxygen saturation measured on ABG analysis and pulse oximeter. Typically, this saturation gap is more than 5% in cases of methaemoglobin.The co-oximeter is an accurate device for measuring methaemoglobin and is the key to diagnosing methemoglobinemia.
Methylene blue is the initial, primary treatment for documented methaemoglobinemia. Dose of methylene blue is 1-2 mg/kg diluted in normal saline as 1% solution and administered intravenously. This dose may be repeated at 1 mg/kg every 30 min as necessary. Maximum dose is 7 mg/kg as this agent in itself can be toxic and cause dyspnoea, chest pain and haemolysis. Non-responders to methylene blue and G6PD deficient patients can be treated with exchange transfusion.
| Conclusion|| |
Patients with methaemoglobinemia can manifest with abnormal presentations perioperatively. With the understanding of various presentations of methaemoglobinemia and their management, these patients can be effectively managed during perioperative period.
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