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Citation: Daar Gh, Soni N, Hummler H, Gupta S, More K. Methemoglobinemia: A rare complication of commonly used topical anaesthetic cream. Jr.

med. res. 2025; 7(1):12-14. Daar et al © All rights are reserved. https://doi.org/10.32512/jmr.7.1.2025/12.14

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Case Report

Daar Ghaniya

, Soni Naharmal

, Hummler Helmut

1,2

, Gupta Samir

1,3

, More Kiran

Dr. Samir Gupta1,3, Dr. Kiran More1

Methemoglobinemia: A rare complication of commonly used topical anaesthetic cream.

1: Sidra Medicine, Pediatric Department,

Neonatology Unit, Doha, Qatar.

2: Weill Cornell Medicine, Doha, Qatar.

3: Durham University, United Kingdom.

* Corresponding Author.

Correspondence to:

ghaniyadaar@gmail.com

Publication Data:

Submitted: December 5, 2024

Accepted: March 12,2025

Online: April 30,2025

This article was subject to full peer-

review.

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Cyanosis is a physical sign stemming from several causes that can develop at any age.

However, its occurrence in the newborn period creates the utmost diagnostic and

treatment challenges due to a very fragile period of the lifespan. Methemoglobinemia

is a condition with life-threatening potential due to diminution of the oxygen-carrying

capacity of circulating hemoglobin. Congenital methemoglobinemia is characterized by

significantly reduced enzymatic activity to transform methemoglobin into functional

hemoglobin. Acquired forms are more commonly seen and usually related to exposure

to certain drugs and agents leading to the increased production of methemoglobin.

We herein report a rare case of acquired methemoglobinemia developed secondary to

the local anesthesia applied for circumcision.

Keywords

Cyanosis; lidocaine; methemoglobinemia; newborn.

Introduction

Methemoglobinemia is a life-threatening hemoglobinopathy related to the oxidation of

divalent ferro-iron of hemoglobin (Hb) to ferri-iron of methemoglobin (MetHb) that

affect oxygen transport. Acquired Methemoglobinemia forms are the most common

and occur due to the exposure to substances that cause oxidation of the Hb directly or

indirectly [1,2].

Observation

A thirteen-day-old male was referred from another facility for circum-oral and

peripheral cyanosis. This was noted by parents six hours after circumcision performed

under local anesthesia: topical anaesthetic cream applied an hour before the

procedure. The patient was born at term, via an uncomplicated vaginal delivery. No

familial history of blood diseases or favism was noted. Weight of 3315g, a length of

51cm and a head circumference of 35.5 cm were recorded. Vital signs were normal.

The patient was pale and dusky with peripheral cyanosis. Cardiac and peripherals

pulses examination was normal. G6PD deficiency and sepsis were ruled out.

Oxygen therapy at 4 L/min was started with mild improvement of the saturation which

variated around 85-88%. Chest X-ray and echocardiography did not reveal any

cyanotic heart disease. Capillary blood gas analysis revealed a methemoglobin level of

46%, lactate 1.6 mmol/L and normal blood electrolyte levels. The diagnosis of

methemoglobinemia was confirmed. Methylene blue of 0.5 mg/kg diluted in Dextrose

5% was given with slow infusion over 10-15 minutes using a filter. The patient

recovered totally and rapidly within 2 hours after the treatment with methylene blue.

All results of capillary blood gas analyses are shown in Table 1.

Abstract

Methemoglobinemia: A rare complication of commonly used topical anaesthetic cream

Citation: Daar Gh, Soni N, Hummler H, Gupta S, More K. Methemoglobinemia: A rare complication of commonly used topical anaesthetic cream. Jr.

med. res. 2025; 7(1):12-14. Daar et al © All rights are reserved. Submit your manuscript: www.jmedicalresearch.com

Before the first dose of

methylene blue

Before the second dose

of methylene blue

One hour after the

second dose

Two hours after the

second dose

7.42

7.43

7.39

7.48

pCO2 (mmHg)

pO2 (mmHg)

Oxygen saturation (%)

99.6

94.4

95.3

92.2

Lactate (mmol/L)

1.6

2.1

2.4

1.2

Hemoglobin (gm/dL)

164

141

156

134

Glucose (mmol/L)

4.7

4.9

5.5

4.6

İonized calcium (mmol/L)

1.38

1.29

1.35

1.41

HCO3 (mmol/L)

23.8

23.5

22.6

25.1

Base excess (mmol/L)

0.4

-1.6

-2.7

0.5

Methemoglobin (%)

46.5

2.2

1.6

Table 1. Capillary blood gas analyses evolution under treatment.

Age/ gender

agent

manifestations

Meth-Hb

Treatment

Larson et al.

(2013)

months/female

EMLA

application over

torso and lower limbs

Seizure

22.8%

Anti-convulsant medication

intravenous methylene blue 1.5

mg/kg

Shachor-Meyouhas

et al. (2008)

28 days/female

EMLA

application over

lower back

32%

IV MB 0.3 mg/kg

Sinisterra et al.

(2002)

months/female

EMLA

application over

both groins to cover an

area of ~8 cm

16%

Double dose of intravenous

methylene blue 2 mg/kg

Couper et al.

(2000)

4 days/ male

EMLA

application over

penis

16%

Elsner et al.

(1997)

7 days/-

EMLA

application over

10 cm

on sacrum, right

buttocks, upper leg

Sleepiness

Kuiper-Prins et al.

(2016)

12 days/ male

EMLA

application over

penis

16%

Oxygen

Jakobson et al.

(1985)

3 months /male

EMLA

application over

back of the hands and in

cubital regions

28%

Intravenous methylene blue 1

mg/kg

Bohnhorst et al.

(2017)

1 day/male

Intravenous lidocaine

infusion

Seizure

13.8%

Oxygen

Gala et al. (2017)

26 days/male

Combination of exogenous

(application of silver

sulfadiazine cream over

umbilicus) and

endogenous (sepsis,

diarrhea and acidosis)

Loose motions,

vomiting and

drowsiness

31%

Intravenous methylene blue2 mg/kg

Erol et al (2017)

1 day,male

Maternal prilocain

administration for

pudendal anesthesia

Cyanosis

40%

Double dose of 300 mg/kg of

ascorbic acid

Table 2: methemoglobinemia treatment literature review.

Discussion

We herein report thirteen-day-old neonate with the diagnosis of methemoglobinemia developed after the application of

lidocaine/prilocaine containing local anesthesia for circumcision. The patient completely recovered following the treatment with

intravenous methylene blue. Neonatal methemoglobinemia can be congenital or acquired. Congenital form reveals

progressively with increasing central cyanosis just after birth [3-5]. This form is related to genetic enzymes deficiency and is

rarely responsive to oxygen therapy. However, acquired methemoglobinemia develops secondary to precipitating agents and

may occur at any time in the neonatal period including birth in case of maternal exposure during delivery [6]. The exposure

causes acceleration of Hb oxidization from the ferrous to the ferric state. Several drugs were reported in methemoglobinemia

cases. The most common drugs are benzocaine and lidocaine [7,8]. Newborn infants are particularly susceptible to the

development of methemoglobinemia because the activity of cytochrome b5 reductase (CYB5R) is lower compared to adult. As

MetHb does not transport oxygen, symptoms are essentially respiratory cardiovascular. Both intravenous ascorbic acid and

methylene blue are effective treatments. Methemoglobinemia should always be considered in the differential diagnosis of

cyanosis in newborns and neonates. Prompt diagnosis and treatment are crucial for complete recovery. Local anaesthetic

including lidocaine/prilocaine should be used with caution for routine circumcision.

Methemoglobinemia: A rare complication of commonly used topical anaesthetic cream

Citation: Daar Gh, Soni N, Hummler H, Gupta S, More K. Methemoglobinemia: A rare complication of commonly used topical anaesthetic cream. Jr.

Conflict of Interest: None

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