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Methemoglobinemia
Related to Local Anesthetics:
A Summary of 242 Episodes
Diana Lee, D.O.
PGY-1
Journal Club
October 21, 2009
Overview
• This article was chosen for discussion as the use of
local anesthetics is quite prevalent and as
anesthesiologist, we need to be aware of the
implications of our treatment and their adverse effects
• This article is a great review of literature on
methemoglobinemia and LAs cases
• Scientific background of this study is discussed for
methemoglobin.
• This article proposes to define safety rules to prevent
LA induced methemoglobinemia
Overview
• Design of this article was a literature search for “local
anesthesia” and “methemoglobinemia” in PubMed that are
written in English or French (as of April 2007; excluded cases
were underlying congenital methemoglobinemia, partial
G6PD deficiency, doubtful diagnosis, no clear relationship to
LA, concomitant drug abuse, high LA administeration
>10mg/kg except benzocaine).
• Dx of metHb was based on at least 1 metHb measurement of
>2%, positive blood test, positive spectroscopic exam, positive
Kronenberg “red-brown” test, cyanosis or low O2 sat value or
cyanosis within a few hrs after administration of a drug know
to cause metHb.
• Total of 242 individual episodes published between 19492007 were analyzed
Summary of findings
• This article found 4 LAs which may have caused methHb
(prilocaine, benzocaine, lidocaine, tetracaine)
• There was a clear difference between SaO2 and PaO2
measurements and metHb. But, low SaO2 in metHb pts
could not reliably predict accurate SaO2; it may
underestimate degree of hypoxia
• Clinical symptoms were observed in low metHb levels
• There was no relationship between the color of the
patients’ skin color and the 1st measurement of metHb
Summary of findings continued…
• Complications of metHb include hypoxic encephalopathy,
MI, or death
• Time to disappearance of clinical cyanosis varied from
0.25 to 9h in pts who received tx (compared to 2-19.8h
for no tx)
• With methylene blue tx, hemolytic anemia and
decrease in SaO2 were seen
Summary of findings continued…
• Prilocaine
• Recommendation of 8mg/kg should be reduced
• metHb seen at lower dosages in children <6mos old,
adult pts on other oxidizing meds, chronic renal
insufficiency, and pregnant women
• Avoid (or reduce the dose) use in the above population
• If using in the above population, use recommended
exposure (e.g for EMLA application) limits and do not
use give it in add’l routes
Summary of findings continued…
• Benzocaine
• Single spray (1sec) of benzocaine can induce metHb, although
exact dosage at which this occur cannot be determined
• However, some children did not demonstrate metHb even at high
concentrations
• Benzocaine reapplication have caused repeated metHb
• Also, rebound metHb related to benzocaine has been seen, even
after a treatment with methylene blue (up to 18h)
• Article concluded that because the response to benzocaine is
unpredictable and there is no “therapeutic window,” it should be
discontinued in all pts
Summary of findings continued…
• Lidocaine
• Though rare, lidocaine, with or without co-administration of
other oxidizing agents, resulted in metHb
• Article recommended use of other LAs in pts taking other
oxidizing meds or pts with congenital methHb
• Tetracaine
• Only one case reported but it may not be the cause of
it, as it was a small dose given over an extended period
of time and clinical symptoms were non-specific
• No clear cause and effect relationship
Summary of findings continued…
• Add’l recommendations…
• Consider DDx for SaO2 saturation and PaO2 differences
(carboxyHb, sulfHb, congenital or acquired diseases
• Definitive Dx of metHb is a measurement by co-oximetry
(simplified spectrophotometer >2.2%)
• Use methylene blue for tx in all pts except for those with G6PD d/f
(use ascorbic acid)
» 0-2mos old  0.5mg/kg IV
» >2mos old  1-2mg/kg over 5min and mix in D5, repeat q 1h to
max 7mg/kg
» Be aware that methylene blue may transiently decrease O2sat
» If refractory, consider blood or exchange transfusion
» Hyperbaric O2 not efficacious
Critique of article
• Good points…
– A thorough literature review on methHb and LAs
that dates back to 1949
– Stated many recommendations on use of the LAs
use and treatments
– Particularly strong on the recommendations for
methylene blue treatment
Critique of article
• Bad points…
– Some of the recommendations included a
recommendation against a drug without specific
parameters
– The method of this article is solely based on
literature search rather than on experimental
trials that consider cause and effect
– Only cases reported in English and French were
included in this article
How does this apply to our practice?
• This article demonstrated rare but real occurrences of metHb
with LAs use
- and, particularly, topical benzocaine is used very commonly in endoscopy
and ET intubations
• MetHb can lead to confusion, cyanosis, hemodynamic
instability, or coma if not recognized and treated
appropriately
• Demonstrated the prevalence of prilocaine associated metHb
that is common in a subset of population (pediatrics, CRI,
pregnant women, pt on oxidizing meds) even at lower levels
of currently recommended drug concentrations. Therefore, a
provider may consider decreasing prilocaine dosing in these
pts.
• This article also stated the importance of monitoring for
rebound metHb
Open discussion……