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 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 h 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……