You are called to the Emergency Department to assist in the management of a 45-year-old man with respiratory distress. He is a known HIV patient with Pneumocystis jiroveci pneumonia and an allergy to sulphonamides.
On examination:
Temperature 38.8ºC
Mucous membranes appear cyanotic
Respiratory rate 35/min
Heart rate 125/min
Blood pressure 90/50 mmHg
SpO2 82% on 8L/min oxygen via Hudson mask
Initial arterial blood gas analysis (ABG) is as follows:
Parameter |
Result |
Normal Range |
pH |
7.32 |
7.35 – 7.45 |
PCO2 |
27.6 mmHg (3.6 kPa) |
35 – 45 (4.6 – 6.0) |
PO2 |
84.6 mmHg (11 kPa) |
|
HCO3 |
13.9 mmol/L |
22 – 27 |
Standard Base Excess |
11.0 |
-2 – +2 |
Hb |
62 G/L |
110 – 165 |
SpO2 |
93.4% |
|
FCOHb |
0.5% |
|
FHHb |
5.4% |
|
FMetHb |
18.4% |
|
FO2Hb |
75.7% |
a)
ABG:
Metabolic acidosis
Respiratory compensation
Anaemia
Marked MetHb
b)
What is the likely diagnosis?
Drug related (dapsone as known sensitivity to sulphonamides) methaemoglobinaemia. Haemolytic anaemia likely in this setting
c)
Outline your management of this patient
ABCs.
Empirical antimicrobial therapy until sepsis is excluded
Cease Dapsone
Use ABG with co-oximetry rather than pulse oximetry in the initial period to monitor response. Oximeter will not be reliable due to MetHb so there will be a reliance on clinical signs and gases.
Optimize tissue oxygen delivery – evidence on ABG that tissue Oxygen delivery is inadequate with lactataemia.
Transfuse - Hb 62 and functionally ~50- transfusion reasonable option
Ensure Hb maximally oxygenated – target high FHbO2 pending resolution of MetHbaemia so pO2 target high (eg >80mmHg)
Methylene Blue infusion 1-2 mg/kg (ideally do a rapid G6PD screen prior)
Exogenous glucose
Exchange transfusion if other measures fail or unavailable
N- acetylcysteine, cimetidine, ketoconazole - experimental
ABG analysis:
Information for the calculation of anion gap and delta ratio is not supplied, but it is irrelevant. The lactate is probably very high. The massive elephant in the room is the methaemoglobinaemia and anaemia, which are causing a significant tissue hypoxia.
The culprit must be dapsone. The man clearly has some sort of chronic suppression therapy for Pneumocystis, and is allergic to sulfonamides. Apart from classical sulfonamides, dapsone is essentially the only dihydrofolate reductase inhibitor useful for this purpose. It is a sufficiently structurally distinct molecule, and many sulfa-allergic people will not react to it
The commonest side effects of dapsone include methaemoglobinaemia, haemolytic anaemia, and agranulocytosis. Dapsone is converted by the cytochrome P-450 system into a hydroxylamine, which then oxidizes haemoglobin - forming methaemoglobin -and in the process regenerates itself back into dapsone, so that the cycle can repeat.
So, how does one treat methaemoglobinaemia?
Ward, Kristina E., and Michelle W. McCarthy. "Dapsone-induced methemoglobinemia." Annals of Pharmacotherapy 32.5 (1998): 549-553.
Wright, Robert O., William J. Lewander, and Alan D. Woolf. "Methemoglobinemia: etiology, pharmacology, and clinical management."Annals of emergency medicine 34.5 (1999): 646-656.