Pharmacology & Poisoning
Question 270 of 300
A 34 year old presents to the Emergency Department complaining of a sore throat. You administer topical benzocaine to allow examination and provide relief. Shortly after you apply the benzocaine the patient becomes tachypnoeic and complains of chest pain. The patient is noted to be cyanotic. Supportive measures are initiated, and a venous gas reveals a methaemoglobin level of 46%. Which of the following should be administered?
Answer:
Local anaesthetics such as benzocaine, lidocaine, and prilocaine can cause an acquired methaemoglobinaemia. Urgent treatment with oxygen and methylene blue is indicated in such patients, especially when accompanied by symptomatic hypoxia (e.g. dysrhythmias, angina, respiratory distress, seizures, coma) and methaemoglobin levels greater than 30%.Methaemoglobinaemia
Pharmacology & Poisoning
Last Updated: 24th February 2023
Pathophysiology
- What is methaemoglobin?
- In normal haemoglobin, iron is in the ferrous (Fe2+) state, which allows binding of oxygen gas (O2) in the lungs and its release to the tissues.
- Methaemoglobin is an altered state of haemoglobin that has been oxidised, changing its haem iron configuration from the ferrous (Fe2+) to the ferric (Fe3+) state. Unlike normal haemoglobin, methaemoglobin does not bind oxygen and as a result cannot deliver oxygen to the tissues.
- In addition, the ferric haem in the haemoglobin tetramer causes the remaining normal ferrous haems within the same haemoglobin molecule to have increased O2 affinity. This produces a left shift of the haemoglobin oxygen dissociation curve and in turn further decreases O2 delivery to the tissues.
- As a result of these two changes (inability to bind oxygen and left-shifting of the oxygen-haemoglobin curve), methaemoglobin causes functional anemia.
- What is methaemoglobinaemia?
- Formation of methaemoglobin and conversion back to the normal ferrous state (by reduction) occurs at low levels during normal red blood cell (RBC) metabolism. Normally, the formation and reduction of methaemoglobin are balanced, and the steady-state level of methaemoglobin is approximately 1 percent of total hemoglobin.
- Clinically significant methaemoglobinaemia occurs when there is an imbalance between two processes, increased production of methaemoglobin or decreased reduction.
- Acquired causes of methaemoglobinaemia are more common than congenital causes. In some cases, an underlying genetic predisposition to methaemoglobin formation can greatly exacerbate methaemoglobinaemia after an exposure to an oxidant.
Causes
Methaemoglobinaemia can be congenital or acquired.
- Congenital
- Cytochrome b5 reductase deficiency
- Haemoglobin M disease
- Cytochrome b5 deficiency
- Acquired
- Dapsone
- Antimalarial agents e.g. chloroquine
- Topical anaesthetics e.g. benzocaine spray
- Inhaled nitric oxide
- Nitrates and nitrites
- Well water, root vegetables, mushrooms, other foods
- Drugs e.g. 'poppers' or 'RUSH' (contain amyl nitrite or isobutyl nitrite)
- Antifreeze
- Aniline dyes and other chemicals
- Certain solvents, dyes, pesticides, and other chemicals
Clinical features
The characteristic presentation of a patient with significant methaemoglobinaemia is persistent cyanosis despite oxygenation.
The methaemoglobin concentration may be related to clinical effects as follows:
- 0-10% - Features unlikely
- 10-30% - Mild effects such as blue-grey 'apparent' central cyanosis (blue to grey lips, tongue and mucus membranes, and slate grey skin), fatigue, dizziness, headaches
- 30-50% - Moderate effects - weakness, tachypnoea, tachycardia
- 50-70% - Severe effects - stupor, coma, convulsions, respiratory depression, cardiac arrhythmias, acidosis
- More than 70% - Potentially fatal
Methaemoglobinaemia should be suspected if:
- The cyanosis fails to respond to oxygen therapy.
- The pO2 is normal in the presence of a decreased measured oxygen saturation on blood gas analysis
- The arterial blood is chocolate brown in colour and remains dark on aeration.
The urine may be discoloured brown or black if methaemoglobinaemia is present.
Management
- Administer high flow oxygen (this may not increase finger probe oxygen saturations).
- Measure the methaemoglobin (MetHb) concentration urgently to confirm diagnosis; usually available on point of care blood gas analysers. Do not delay treatment if MetHb concentration is not available or delayed. Blood samples for MetHb measurement should be analysed as soon as possible after collection.
- The decision to administer methylthioninium chloride (methylene blue) is based on clinical features and the MetHb concentration. For adults and children aged 3 months older:
- Severe methaemoglobinaemia
- If MetHb concentration is greater than 45% OR
- Patient has severe features of methaemoglobinaemia
- Give methylthioninium chloride 2 mg/kg IV slowly over 5 minutes
- Less severe methaemoglobinaemia
- If patient has mild to moderate features of methaemoglobinaemia OR
- MetHb concentration is between 30 and 45% with or without symptoms OR
- MetHb concentration is less than 30% AND patient has a pre-existing disease that increases the susceptibility to tissue hypoxia (e.g. anaemia, pulmonary disease, heart failure)
- Give methylthioninium chloride 1 mg/kg IV slowly over 5 minutes
- Severe methaemoglobinaemia
- If no response to treatment repeat dose in 30 minutes. Continue to monitor MetHb concentration every 60 minutes after therapy to assess effectiveness, or sooner if cyanosis recurs. Note that methaemoglobinaemia may recur and further treatment may be required. Dosing can be complicated and methylthioninium chloride doses in excess of 4 mg/kg should not be given without prior discussion with NPIS
- When treatment with methylthioninium chloride is ineffective or contraindicated, exchange transfusion should be considered. If this is not available, consider immediate administration of O-negative red cells to increase oxygen carrying capacity of blood. Continue to monitor MetHb concentration.
- Other measures as indicated by the patient's clinical condition.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
