A Case of Methemoglobinemia Thought to Have Been Caused by the Combined Use of Propitocaine and Nitroglycerin During General Anesthesia

Acquired methemoglobinemia can occur following exposure to oxidizing agents including high doses of certain local anesthetics.¹ Many studies have investigated the dose at which each causative drug causes methemoglobinemia. However, few studies have reported methemoglobinemia being caused by the combined use of causative drugs or agents.² This is a report of a methemoglobinemia case presumably caused by the combined use of prilocaine (propitocaine in Japan) and nitroglycerin (NTG) during general anesthesia.

CASE REPORT

A 39-year-old woman (height 163.7 cm; weight 51.3 kg; body mass index 19.2 kg/m²) required bimaxillary surgery for a jaw deformity. She had been diagnosed with schizophrenia and was under treatment with aripiprazole (Abilify tablets; 3 mg/d), which has an α₁-blocking effect. Therefore, we elected to avoid the use of lidocaine with epinephrine and instead chose prilocaine with felypressin for infiltrative local anesthesia.

General anesthesia was induced and maintained with boluses of fentanyl (total dose 600 μg), continuous infusions of remifentanil (0.15–0.4 μg/kg/min) and propofol (target blood concentration 2.5–5 μg/mL using target-controlled infusion pump), and intermittent boluses of rocuronium (total dose 190 mg). She was successfully intubated with a 6.5-mm preformed nasal endotracheal tube, and her percutaneous arterial oxygen saturation (SpO₂) was 100% on oxygen (1 L/min) and air (2 L/min). After the administration of 10 mL of 3% prilocaine (300 mg) with felypressin (0.3 units) for local anesthesia via infiltration, a continuous infusion of NTG (0.5 μg/kg/min) was started for intentional hypotensive anesthesia. After 15 minutes, her SpO₂ level had decreased to 96%. A repeat arterial blood gas sample was obtained for comparison with one taken previously, which showed that her methemoglobin level had increased from 0.7% (baseline) to 3.5%. The patient was then diagnosed with methemoglobinemia, the hypotensive anesthetic agent was changed from NTG (total dose 1.265 mg) to prostaglandin E1, and a bolus of 1% methylene blue (60 mg) was administered intravenously to treat the methemoglobinemia (Figure). Approximately 20 minutes later, her SpO₂ level recovered to 99% and methemoglobin levels decreased to 1.0% as noted on a repeat arterial blood gas. Subsequently, the local anesthetic was changed and 8 mL of 1% lidocaine (80 mg) with 1:200,000 epinephrine (0.04 mg) administered intraoperatively for infiltrative local anesthesia throughout the remainder of the case. There were no further increases in her methemoglobin levels or episodes of SpO₂ decreases during the perioperative period, nor were any other complications noted throughout her stay and ensuing discharge from the hospital.

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DISCUSSION

The patient described herein likely developed methemoglobinemia from the combined use of prilocaine and NTG. Methemoglobinemia can occur with large doses of causative oxidizing agents, such as prilocaine and NTG (Table).¹ However, in this case, the patient was administered a total of 300 mg (5.85 mg/kg) of prilocaine and 1.265 mg (0.5 μg/kg/min) of NTG. Those total doses did not exceed 8 mg/kg³ and 3 μg/kg/min⁴, respectively, which are the doses that have been reported to increase the risk of methemoglobinemia. However, methemoglobinemia nonetheless occurred in this patient, suggesting the combined use of causative drugs to be the likely contributing factor.

Table.  Predisposing Drugs That May Cause Methemoglobinemia

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Lidocaine is also a causative drug for methemoglobinemia.¹ However, reports of lidocaine-induced methemoglobinemia are extremely rare compared with those of prilocaine-induced methemoglobinemia.⁵ Therefore, in this case, the local anesthetic was changed from prilocaine to lidocaine in an effort to avoid continuation of the methemoglobinemia event following the supplemental use of local anesthetics intraoperatively.

CONCLUSION

The combined use of causative drugs may increase the risk of methemoglobinemia occurring despite individual drug dosages remaining below the recommended triggering threshold.

This research was originally published in the Journal of the Japanese Dental Society of Anesthesiology, 2019;47(3):110–112.