A Case of Severe Hypoxia Caused by Phenazopyridine-Induced Methemoglobinemia: A near Fatal Event from Over-the-Counter Medication Use
Round 1
Reviewer 1 Report
Overall well written, no obvious flaws detected
Author Response
Comments and Suggestions for AuthorsOverall well written, no obvious flaws detected
Response: Thank you so much for the reviews
Reviewer 2 Report
I would like to congratulate the authors on completing this interesting case report. I only have a few comments
1. Avoid repeating lines 28-30 (introduction) in the discussion part. Can shorten the introduction sentence and elaborate in discussion
2. Lines 62-63 should say refractory hypoxia, as she had normal, rather supernormal partial tension of oxygen in her blood (not hypoxemic).
3. Was G6pD checked before methylene blue was administered in this patient?
4. Another interesting aspect of this is that in the listed review of cases (Table 3), patients had a variable duration of intake of phenazopyridine before developing methemoglobinemia. Could authors comment on this in the discussion? is it related to age, renal function, underlying comorbidities or perhaps some inherent predisposition to the development of methemoglobinemia?
Author Response
I would like to congratulate the authors on completing this interesting case report. I only have a few comments
1.Avoid repeating lines 28-30 (introduction) in the discussion part. Can shorten the introduction sentence and elaborate in discussion
Response: The introduction sentences 28-30 as been shortened and it has been elaborate in discussion section as below:
Introduction: However, most cases are acquired induced by exogenous substances such as medications, chemicals, and environmental substances [4].
Discussion: Acquired methemoglobinemia is more common than congenital methemoglobinemia, which is caused due to various oxidizing substances such as medications (dapsone, chloroquine, primaquine, nitroglycerin, rasburicase, topical anesthetics such as benzocaine and lidocaine, sulfonamides, phenazopyridine) and chemical and environmental substances (anilines dyes, antifreeze, benzene derivatives, nitrates, and nitrites, hydrogen peroxide, paraquat, chorates, naphthalenes) [4]
- Lines 62-63 should say refractory hypoxia, as she had normal, rather supernormal partial tension of oxygen in her blood (not hypoxemic).
Response: Refractory hypoxemia has been corrected to refractory hypoxia.
- Was G6pD checked before methylene blue was administered in this patient?
Response: G6PD was not checked before the administration of methylene blue as she was critically ill, and the test result would have taken 2-3 days. However, the patient was closely monitored for hemolysis and responded well to methylene blue with no evidence of hemolysis that suggested she did not have G6PD deficiency.
The above statement has been added to discussion section lines 122-124.
- Another interesting aspect of this is that in the listed review of cases (Table 3), patients had a variable duration of intake of phenazopyridine before developing methemoglobinemia. Could authors comment on this in the discussion? is it related to age, renal function, underlying comorbidities or perhaps some inherent predisposition to the development of methemoglobinemia?
Response: The various patient factors such as chronic kideny disease, heart and lung disease,anemia,and inherent enzymes such as G6PD deficiency, cytochrome b5 reductase (Cyb5R) deficiency or heterozygotes variant with lower than average baseline activity increasse suspectibility for phenozopyridine induced methemoglobinemia. Hence, methemoglobinemia could occur with variable amount and duration of intake of phenazopyridine as demonstrated in table 3.
Added reference 16. Iolascon A, Bianchi P, Andolfo I, Russo R, Barcellini W, Fermo E, Toldi G, Ghirardello S, Rees D, Van Wijk R, Kattamis A. Recommendations for diagnosis and treatment of methemoglobinemia. Am J Hemat. 2021;96(12):1666-78.
The above statement has been added to discussion section lines 108-112 and reference line 193-194
Reviewer 3 Report
The case report has been well written.
Kindly include race/ethnicity of the patient.
Should also include if the patient had any prior history of such reactions? Kindly also include if the patient had any history of drug allergies.
Kindly correct temperature degree symbol on page 57 line 45.
Author Response
The case report has been well written.
Kindly include race/ethnicity of the patient.
Response: A 89-year-old white female has been added
Should also include if the patient had any prior history of such reactions? Kindly also include if the patient had any history of drug allergies.
Response: She had no previous history of similar presentation, and the review of drug allergies was unremarkable except for an allergic rash with nitrofurantoin.
Kindly correct temperature degree symbol on page 57 line 45.
Respone: the degree symbol has been corrected
