Methaemoglobinaemia in the perioperative period with regional block

Background

Methaemoglobin is a form of haemoglobin with oxidised ferric (+3) iron rather than ferrous (+2) iron.1 Haemoglobin with ferric iron is unable to reversibly bind oxygen and additionally causes remaining functional ferrous iron groups to have an increased affinity for oxygen.1 These effects cause a leftward shift in the oxyhaemoglobin dissociation curve and prevents oxygen delivery to peripheral tissues and organs.1 With increasing impairment of oxygen delivery based on methaemoglobin level, patients can have a range of symptoms from mild cyanosis and dyspnoea at low levels progressing to shock, severe respiratory depression, seizures and coma at high levels.1 Signs include hypoxia without improvement with oxygen supplementation, cyanosis of the skin, lips and nail beds despite normal arterial oxygen pressure (PaO₂) and blood discolouration with dark red or chocolate colour without improvement with oxygen.1 2 Methaemoglobinaemia can be congenital or acquired with various pre-existing medical conditions such as cardiovascular disease, respiratory disease and anaemia increasing susceptibility to symptomatic methaemoglobinaemia.1 2 Anaesthesia providers need to be familiar with this differential diagnosis for hypoxia given the use of drugs in the perioperative setting known to induce methaemoglobinaemia, including drugs such as benzocaine and lidocaine, antibiotics such as dapsone and anaesthetic gases, including nitric oxide.1 This case report presents an interesting case of methaemoglobinaemia in the perioperative period in the setting of dapsone use and preoperative regional erector spinae nerve block.

Case presentation

An 81-year-old man with a medical history significant for hypertension, smoking history of 80 pack-year, chronic obstructive pulmonary disease (COPD), coronary artery disease (CAD) with two drug-eluting stents, bladder cancer status post cystectomy with ileal conduit, peristomal bullous pemphigoid and known right renal stone burden presented for right percutaneous nephrostomy tube placement in February 2021. Anaesthetic plan included general anaesthesia with preoperative erector spinae block for postoperative pain control. After consent was obtained, the patient was attached to monitors before beginning the right-sided erector spinae block with oxygen saturation (SpO₂) noted to be 92%–93%, which was attributed to his COPD. After timeout was performed, the patient was given 25 mcg of fentanyl for comfort during block placement due to anxiety. The erector spinae block was performed with 5 mL of lidocaine for skin localisation and 30 mL of ropivacaine under ultrasound guidance with good visualisation of the needle tip and local spread (refer to figure 1).

Around 15 min after block placement, the patient’s SpO₂ drifted down between 88% and 89% with intermittent desaturations to 84%–85%. He was placed on nasal cannula with SpO₂ remaining at 88%–89% despite uptitration of oxygen to 6 L/min. On examination, lips were noted to be cyanotic with mild tachypnoea but with good bilateral breath sounds. The case was delayed and a chest X-ray revealed no pneumothorax. An arterial blood gas (ABG) was obtained at the bedside and was noted to be dark with the following results: pH: 7.41, partial pressure of carbon dioxide: 33.8, PaO₂: 74.6 and HCO_3⁻ : 21.

Differential diagnosis

On further history, the patient revealed being recently started on dapsone for his peristomal bullous pemphigoid, which he began in late November 2020. This history was not obtained initially in the preoperative interview and was not in his medication list. He was being followed by dermatology team, but pulse oximetry was not checked during their clinic visits. He had a urology preoperative visit since starting dapsone with SpO₂ of 92%, which was 1 week before surgery. Given history of dapsone use and no improvement in SpO₂ with supplemental oxygen, a methaemoglobin level was obtained and came back elevated at 8.8% (normal level: <1%).

In this case, diagnosis was delayed due to an inaccurate medication list, especially since dapsone is a known offending agent.1 3 There also were other confounding possibilities for desaturation in the setting of chronic medical conditions and sedation given during block placement. His initial SpO₂ of 93% was attributed to his known COPD and he had a SpO₂ of 92% at his preoperative visit. The patient also received 25 mcg of fentanyl just prior to block placement. Opioid use in older patients and those with respiratory disease can cause respiratory depression.4 However, our patient never became somnolent, was alert and oriented throughout the procedure, and never developed shallow, slow breathing pointing away from an overdose of opioid medication. Additionally, opioid-indued hypoxia would likely have improved with supplemental oxygen.

Per the Stanford Anesthesia Emergency Manual, the differential diagnosis for hypoxemia includes hypoventilation, low fractional inspired oxygen (FiO₂), V/Q mismatch or shunt, diffusion problem and increased metabolic oxygen demand.5 The patient’s respiratory rate was mildly tachypnoeic at 24–26 breaths/min and breath sounds were equal bilaterally pointing away from hypoventilation. The facemask on the patient was hooked to an oxygen tank, which was checked and working properly, so low FiO₂ was not likely contributing. For V/Q mismatch and shunt, the patient’s CXR was normal making pathologies such as atelectasis, pleural effusion, mucus plugging or pneumothorax extremely unlikely.5 Diffusion abnormality typically occurs in chronic lung disease.5 The patient had COPD, so he likely had a baseline diffusion abnormality. This may have contributed to him becoming hypoxaemic at lower methaemoglobin levels compared with healthy individuals. Finally, increased metabolic demand can occur in thyrotoxicosis, sepsis and hyperthermia, which were not present in this patient.5

Once ruling out the common causes of hypoxaemia, providers need to consider less common diagnoses such as methaemoglobinaemia. Checking an ABG allows for acid–base analysis as well as the calculation of an oxygen saturation gap, which is the difference between the calculated oxygen saturation from a standard blood gas machine and pulse oximetry reading. If the oxygen saturation gap is greater than 5%, abnormal forms of haemoglobin such as methaemoglobinaemia, carboxyhaemoglobinaemia or sulfhaemoglobinemia need to be considered.3 6 The calculated oxygen saturation on the ABG was 93.3% and the patient’s pulse oximetry was between 84%–88%. His oxygen saturation gap was >5% and pointed towards a diagnosis of symptomatic methemoglobinemia. Methemoglobinemia can also lead to a gap metabolic acidosis on ABG due to lactic acidosis.6 This patient’s pH and HCO_3- were normal at 7.41 and 21, respectively, however his oxygen delivery may not have been severe enough to lead to impaired tissue oxygenation and lactate production.

Treatment

Once methaemoglobinaemia is identified, initial treatment involves stopping the offending substance.1 In this incident, dapsone was stopped and supportive care, including supplemental oxygen, was administered. Methylene blue is used in symptomatic patients with methaemoglobin level <20% or in asymptomatic patients with methaemoglobin level >30%.1 Methylene blue is typically preferred over ascorbic acid due to better speed and effectiveness.1 Consultation with pulmonology, cardiology and haematology teams may be needed, especially in patients with comorbidities such as the reported patient, to help with treatment plan.1 In this case, pulmonology was consulted. It was recommended for the patient to continue supportive care with supplemental oxygen and to discontinue dapsone. Methylene blue was not recommended given the patient’s methaemoglobin level was below 10%.

Outcome and follow-up

After a multidisciplinary discussion with pulmonology, anesthesiology and urology teams, the decision was made to cancel the procedure and monitor overnight. The patient was able to be weaned off supplemental oxygen by discharge with SpO₂ stable at 92%–93%. He came back a week later for right percutaneous nephrostomy tube placement. Notably, patient’s SpO₂ had improved to 95%–96% after dapsone being held for a week. A erector spinae block was not performed prior to the procedure and the case was successful without issue. Multimodal pain medications, including acetaminophen and oxycodone, were used for postoperative pain control. The patient went for dermatology follow-up and was transitioned to methotrexate 10 mg weekly for peristomal bullous pemphigoid.