Methemoglobinemia Related to Local Anesthetics: A Summary of 242 Episodes

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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

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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

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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 gt10mg/kg except benzocaine).
• Dx of metHb was based on at least 1 metHb
  measurement of gt2, 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 1949-2007 were analyzed

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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

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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

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Summary of findings continued

• Prilocaine
• Recommendation of 8mg/kg should be reduced
• metHb seen at lower dosages in children lt6mos
  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 addl routes

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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

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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

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Summary of findings continued

• Addl 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 gt2.2)
• 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
• gt2mos 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

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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

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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

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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

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Open discussion