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Three Part Question

In [adults with methaemoglobinaemia due to local anaesthetic use] is [methylene blue better than placebo] at [reducing morbidity and mortality]?

Clinical Scenario

A patient has received a benzocaine spray for pain relief during insertion of a nasogastric tube, soon after he becomes remarkably cyanosed. methaemoglobinaemia is diagnosed. What would be the best treatment option for him?

Search Strategy

Using Ovid interface; Medline 1950 to June week 4 2010, Embase 1980 to 2010 week 26, Cochrane database of systematic reviews 2005 May 2010
[exp methemoglobin$/ OR methaemoglobin$.mp.] AND [methylene blue.mp. OR exp Methylene Blue/OR Methylthioninium chloride.mp.] AND [exp Anesthesia, Local/ OR (local adj1 anaesthe$).mp OR exp Anesthetics, Local/ OR exp bupivacaine/ OR bupivacaine$.mp. OR lidocaine/ OR lidocaine$.mp. OR exp prilocaine/ OR prilocaine$.mp. OR exp lignocaine/ OR lignocaine$.mp. OR marcaine$.mp.] LIMIT to English language and humans.

Search Outcome

295 papers found 7 of which were relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Guay J 2009 Canada	242 patients (160 adults) with methaemoglobinaemia due to local anaesthetics.	Meta-analysis	Patients recovering after Methylene Blue administered	Authors advice methylene blue should be first line treatment in those without glucose-6-phosphate deficiency.	Search methods limited. Only one database used and references checked. Explicit methods for inclusion not stated. Only why some studies were not included. Methodological quality not assessed
Young B 2008 USA	27 year old male with methaemoglobinaemia due to use of benzocaine oral spray.	Case report	Patient recovering after Methylene Blue administered.	Patient fully recovered after methylene blue administered.	No report of long term follow up.
Lin S et al 2007 China	48 year old female with methaemoglobinaemia after benzocaine spray use. Received 70 mg of 1% methylene blue over five minutes.	Case report	Patient recovering after Methylene Blue administered.	Patient fully recovered after methylene blue administered.	No long term follow up offered.
Adams V et al 2007 England	45 year old female receiving prilocaine for dental procedure, causing methaemoglobinaemia. 43 mg methylene blue unspecified concentration administered.	Case report	Patients recovering after Methylene Blue administered	Patient fully recovered after methylene blue administered.	No long term follow up. Concentration of methylene blue not discussed.
Jiminez M et al 2007 USA	56 year old female recieved benzocaine spray which caused methaemoglobinaemia. Administered methylene blue 60 mg over 5 minutes, unknown concentration.	Case report	Patients recovering after Methylene Blue administered	Patient fully recovered after methylene blue administered.	Patient not adequately described. No long term follow up. Preceding events not adequately described.

Comment(s)

The search revealed good evidence for the use of methylene blue to treat methaemoglobinaemia caused by local anaesthetics. Although the evidence was retrieved from case studies, there were over 200 positive reports on its successful use. It must be noted that in patients suffering from glucose-6-phosphate deficiency methylene blue will not work and may cause haemolytic anaemia.

Clinical Bottom Line

Methylene blue should be used as the first line treatment for those suffering from methaemoglobinaemia due to local anaesthetic toxicity.

References

1. Guay J Methemoglobinemia related to local anesthetics: A summary of 242 episodes. Anesth Analg. 2009 Mar;108(3):837-45.
2. Young B Intraoperative detection of methemoglobinemia in a patient given benzocaine spray to relieve discomfort from a nasogastric tube: A case report. AANA J. 2008 Apr;76(2):99-102.
3. Lin S et al Methemoglobinemia induced by exposure to topical benzocaine for an awake nasal intubation - A case report. Acta Anaesthesiol Taiwan. 2007 Jun;45(2):111-6.
4. Adams V et al Prilocaine induced methaemoglobinaemia in a medically compromised patient. Was this an inevitable consequence of the dose administered?. Br Dent J. 2007 Nov 24;203(10):585-7.
5. Jiminez M et al Methemoglobinemia and transesophageal echo. Proc West Pharmacol Soc. 2007;50:134-5.