The Story of The Blue and The BlueThe Story of The Blue and The Blue

The Story of the Blue and the The Story of the Blue and the BlueBlue

Morbidity and Mortality ConferenceMorbidity and Mortality ConferenceShadwan Alsafwah, MDShadwan Alsafwah, MD

Cardiology fellowCardiology fellowThe University of Tennessee at MemphisThe University of Tennessee at Memphis

CaseCase 44 Y/O M with hx of cocaine and ETOH abuse presented to 44 Y/O M with hx of cocaine and ETOH abuse presented to

the ED with few weeks history of right foot pain with foul the ED with few weeks history of right foot pain with foul smelling discharge, fevers at home, and feeling ill smelling discharge, fevers at home, and feeling ill

PMH: PMH: HTN HTN IDDM with CRI and BLE neuropathy IDDM with CRI and BLE neuropathy Gastric CA Gastric CA PUD PUD PSH:PSH: Billirouth II surgery in 2004Billirouth II surgery in 2004 Ray amputation of left 3Ray amputation of left 3rdrd toe toe SH:SH: Cocaine and ETOH abuse, with recent bingeCocaine and ETOH abuse, with recent binge smokes 2-3 cig/day since age 14smokes 2-3 cig/day since age 14

CaseCase Meds: Meds: Was not taking any of his meds:Was not taking any of his meds: HCTZHCTZ FelodipineFelodipine InsulinInsulin Omeprazole Omeprazole Allergies:Allergies: NKDANKDA FH:FH: Positive for DM and HTNPositive for DM and HTN ROS: ROS: Other than the R foot pain and fever, was negative Other than the R foot pain and fever, was negative

CaseCase Physical Exam:Physical Exam: 204/106, 15, 105, 100.3, 97% on RA 204/106, 15, 105, 100.3, 97% on RA Head: NC, ATHead: NC, AT ENT: dry mucous membranesENT: dry mucous membranes Neck: No JVDNeck: No JVD Chest: CTABChest: CTAB CVS: tachycardic, RRR, accentuated A2, no murmurs, CVS: tachycardic, RRR, accentuated A2, no murmurs,

no gallopsno gallops Abdomen: midline scar, soft, NT, ND, NABSAbdomen: midline scar, soft, NT, ND, NABS Ext: R foot: inflamed 2-5 toes, eschar on planter Ext: R foot: inflamed 2-5 toes, eschar on planter surface of the great toe, (+) surface of the great toe, (+)

subcutaneous gas subcutaneous gas

CaseCase

Labs: Labs: WBC 35,500 Hem 9 HCT 27.3 (at baseline) Plt WBC 35,500 Hem 9 HCT 27.3 (at baseline) Plt

573000 573000 MCV 70 MCV 70 Na 118 K 4.4 CL 80 HCO3 22.7 BUN 69 Cr 4.9 Na 118 K 4.4 CL 80 HCO3 22.7 BUN 69 Cr 4.9

(baseline 2.4) Glucose 585(baseline 2.4) Glucose 585 Lactate 1.4Lactate 1.4 Urine: (+) ketonesUrine: (+) ketones tox screen: (+) cocaine tox screen: (+) cocaine Right foot X-ray: (+) gas in the soft tissue of the 2Right foot X-ray: (+) gas in the soft tissue of the 2ndnd

and 3and 3rdrd toes toes

CaseCase Admitted to SICU to Surgery Service with Medicine Admitted to SICU to Surgery Service with Medicine

on consult and was started on:on consult and was started on: IVFIVF Insulin dripInsulin drip Broad spectrum Abx (Pip/Tazo and Vanc)Broad spectrum Abx (Pip/Tazo and Vanc) BP control (labetolol, felodipine)BP control (labetolol, felodipine) Had transmetatarsal amputation the same day Had transmetatarsal amputation the same day His blood cultures grew: MRSA and Beta hemolytic His blood cultures grew: MRSA and Beta hemolytic

Strep Strep POD#5: started to have temp spikes POD#5: started to have temp spikes U/A, CXR were negative U/A, CXR were negative Repeat blood cultures and urine cultures were Repeat blood cultures and urine cultures were

negative (on Abx)negative (on Abx)

CaseCase 2D echo requested to R/O endocarditis, showed:2D echo requested to R/O endocarditis, showed: Normal LVSF, EF 70%Normal LVSF, EF 70% Normal chamber sizesNormal chamber sizes Mild concentric LVHMild concentric LVH Possible diastolic dysfunctionPossible diastolic dysfunction Mild-mod TR, mild MR, mild AI, mild PIMild-mod TR, mild MR, mild AI, mild PI Mild pulmonary HTN (peak systolic PAP 40 mmHg)Mild pulmonary HTN (peak systolic PAP 40 mmHg) Mild nodular thickening of the anterior tricuspid Mild nodular thickening of the anterior tricuspid

leaflet seen on the apical 4-chamber view, leaflet seen on the apical 4-chamber view, suspicious but not definite for vegetationsuspicious but not definite for vegetation

TEE may be indicated if clinical suspicion is strong TEE may be indicated if clinical suspicion is strong

CaseCase TEE was scheduledTEE was scheduled The patient was kept NPO post midnight The patient was kept NPO post midnight His PE on the morning of the TEE exam:His PE on the morning of the TEE exam: 157/91, 103, 15, Temp 100.7, Sat 97% on RA157/91, 103, 15, Temp 100.7, Sat 97% on RA Neck: no JVDNeck: no JVD Chest: CTABChest: CTAB CVS: RRR, No murmursCVS: RRR, No murmurs Abdomen: soft, NT, ND, NABSAbdomen: soft, NT, ND, NABS Ext: S/P R TMT amp.Ext: S/P R TMT amp. Labs: Labs: WBC 11.300 Hemog 8.4 HCT 25.8 PLT 518WBC 11.300 Hemog 8.4 HCT 25.8 PLT 518 Na 133 K 3.7 CL 100 HCO3 25.7, BUN 36 Cr 2.8 Na 133 K 3.7 CL 100 HCO3 25.7, BUN 36 Cr 2.8

Glucose 122 Glucose 122 Coags WNLCoags WNL

CaseCase Prep for TEE included:Prep for TEE included: Lidocaine hydrocholoride 2% viscous 20 ml x 2 Lidocaine hydrocholoride 2% viscous 20 ml x 2 Benzocaine 20% spray (Hurricaine) x2Benzocaine 20% spray (Hurricaine) x2 O2 2L/min NCO2 2L/min NC Conscious sedation included: Conscious sedation included: Meperidine (Demerol) 25 mg IVPMeperidine (Demerol) 25 mg IVP Midazolam (Versed) 2 mg IVPMidazolam (Versed) 2 mg IVP The patient experienced discomfort and nausea The patient experienced discomfort and nausea

when the TEE probe introduction was attempted, when the TEE probe introduction was attempted, so 2 more sprays of Benzocaine were administeredso 2 more sprays of Benzocaine were administered

The TEE probe was eventually advanced, and the The TEE probe was eventually advanced, and the study started study started

CaseCase After 10 minutes, the patient became cyanotic, After 10 minutes, the patient became cyanotic,

O2 Sat by pulse oximetry dropped down to 89%O2 Sat by pulse oximetry dropped down to 89% O2 increased to 6L NC. However the pt became O2 increased to 6L NC. However the pt became

tachypnic, more cyanotic and pulse ox dropped tachypnic, more cyanotic and pulse ox dropped further to 85% further to 85%

PE: cyanotic, tachypnicPE: cyanotic, tachypnic Vitals: 165/95, 25, 120s, Sat 85% on 6LNC Vitals: 165/95, 25, 120s, Sat 85% on 6LNC ENT: no stridorENT: no stridor Lungs: CTABLungs: CTAB CVS: tachycardic, RRRCVS: tachycardic, RRR Neuro: sedated/obtundedNeuro: sedated/obtunded Monitor: sinus tachycardia Monitor: sinus tachycardia

What Happened!!!What Happened!!!

Narcotic/benzodiazepine induced Narcotic/benzodiazepine induced respiratory depression! respiratory depression!

Brochospasm/aspiration! Brochospasm/aspiration! Esophageal rupture!Esophageal rupture! Something else!!!Something else!!!

CaseCase The procedure was terminatedThe procedure was terminated Flumazenil (romazicon) 0.2 mg IVP x2 Flumazenil (romazicon) 0.2 mg IVP x2 Naloxone (narcan) 1 mg IVP were givenNaloxone (narcan) 1 mg IVP were given 100% NRM administered, but the patient remained 100% NRM administered, but the patient remained

cyanotic, obtunded with pulse oximetry still 85%!!!cyanotic, obtunded with pulse oximetry still 85%!!! Anesthesia and respiratory care were called for Anesthesia and respiratory care were called for

emergent intubation emergent intubation CXR ordered statCXR ordered stat ABGS blood drawn and sent was noted dark brown ABGS blood drawn and sent was noted dark brown

in color, so it was repeated even before waiting for in color, so it was repeated even before waiting for the results:the results:

7.49/31.2/363.1/25/100% 7.49/31.2/363.1/25/100%

CaseCase Methemoglobinemia was suspected Methemoglobinemia was suspected IV methylene blue at 1 mg/kg IVP was given IV methylene blue at 1 mg/kg IVP was given

in the echo lab in the echo lab Pt. responded well with quick reversal of his Pt. responded well with quick reversal of his

MS changes, cyanosis, and hypoxemia MS changes, cyanosis, and hypoxemia Was transferred to ICU for close observationWas transferred to ICU for close observation Blood was sent out for Methemoglobin level Blood was sent out for Methemoglobin level

which came back later: Methemoglobin level which came back later: Methemoglobin level 31% (reference range: 0.4-1.5%) 31% (reference range: 0.4-1.5%)

The patient did well overnight and the next The patient did well overnight and the next morning repeat Methemoglobin level was morning repeat Methemoglobin level was 0.9% 0.9%

OutlineOutline

Safety of TEESafety of TEE Historical Historical

backgroundbackground Physiologic Physiologic

backgroundbackground PathophysiologyPathophysiology MethemoglobinemiMethemoglobinemi

a typesa types Benzocaine Benzocaine

formulationformulation

Risk factorsRisk factors Clinical Clinical

presentationpresentation DiagnosisDiagnosis TreatmentTreatment ConclusionConclusion

Daniel et al. Safety of Transesophageal Echocardiography. Circulation 1991;83:817-821

Khandheria et al. Mayo Clin Proc 1994; 69:856-863

Historical Background & Historical Background & IncidenceIncidence

The first case of benzocaine induced The first case of benzocaine induced methemoglobinemia was documented by Bernstein methemoglobinemia was documented by Bernstein in 1950in 1950

Up to 1994 fewer than 100 cases has been Up to 1994 fewer than 100 cases has been reported in literaturereported in literature

Between Nov 1997 through March 2002, 132 cases Between Nov 1997 through March 2002, 132 cases of benzocaine induced methemoglobinemia was of benzocaine induced methemoglobinemia was reported to FDA :reported to FDA :

107 serious (81.1%) 107 serious (81.1%) 2 deaths (1.5%) 2 deaths (1.5%) In the pulmonary literature topical anesthetics In the pulmonary literature topical anesthetics

(benzocaine and lidocaine) induced (benzocaine and lidocaine) induced methemoglobinemia occurred in an incidence of methemoglobinemia occurred in an incidence of 1/7000 bronchoscopies1/7000 bronchoscopies

Physiologic BackgroundPhysiologic Background

Hemoglobin contains 4 heme groups with each containing an iron in it’s ferrous state (Fe2+)

Physiologic BackgroundPhysiologic Background

It is this ferrous state (Fe 2+) that allows It is this ferrous state (Fe 2+) that allows O2 to be transported and delivered to O2 to be transported and delivered to the tissues.the tissues.

With 4 heme groups having an iron in With 4 heme groups having an iron in the ferrous state, one O2 molecule may the ferrous state, one O2 molecule may be carried on each heme.be carried on each heme.

Methemoglobin is an altered state of Methemoglobin is an altered state of hemoglobin in which the ferrous (Fe2+) hemoglobin in which the ferrous (Fe2+) irons of heme are oxidized to the ferric irons of heme are oxidized to the ferric (Fe3+) state (Fe3+) state

PathophysiologyPathophysiology

The ferric hemes of methemoglobin The ferric hemes of methemoglobin are unable to bind and carry oxygen, are unable to bind and carry oxygen, resulting in functional anemiaresulting in functional anemia

In addition, the oxygen affinity of In addition, the oxygen affinity of any accompanying ferrous hemes in any accompanying ferrous hemes in the hemoglobin tetramere is the hemoglobin tetramere is increasedincreased

As a result, the oxygen dissociation As a result, the oxygen dissociation curve is left shifted, and oxygen curve is left shifted, and oxygen delivery to the tissues is impaired delivery to the tissues is impaired

Methemoglobin

PathophysiologyPathophysiology

RBC are continuously subjected to RBC are continuously subjected to oxidative stressors that result in the oxidative stressors that result in the formation of methemoglobin formation of methemoglobin spontaneously in normal individuals at spontaneously in normal individuals at a rate of 0.5-3% of the available a rate of 0.5-3% of the available hemoglobin per dayhemoglobin per day

Reduction of methemoglobin maintains Reduction of methemoglobin maintains a steady state level of methemoglobin a steady state level of methemoglobin of about 1% of total hemoglobinof about 1% of total hemoglobin

PathophysiologyPathophysiology The most physiologically important pathway The most physiologically important pathway

for reducing methemoglobin back to for reducing methemoglobin back to hemoglobin is the NADH-dependent reaction hemoglobin is the NADH-dependent reaction catalyzed by methemoglobin reductase catalyzed by methemoglobin reductase enzyme [cytochrome b5 reductase (b5R)], enzyme [cytochrome b5 reductase (b5R)], this accounts for 95% of the reducing activitythis accounts for 95% of the reducing activity

Less important alternative pathway in Less important alternative pathway in Methemoglobin reduction is by an enzyme Methemoglobin reduction is by an enzyme utilizing NADPH pathway utilizing NADPH pathway

Glutathione and ascorbic acid are slow-acting Glutathione and ascorbic acid are slow-acting pathways that play minor roles in the direct pathways that play minor roles in the direct reduction of methemoglobin reduction of methemoglobin

Methemoglobinemia Methemoglobinemia TypesTypes

Methemoglobinemia occurs when an imbalance due Methemoglobinemia occurs when an imbalance due to either increased methemoglobin production or to either increased methemoglobin production or decreased methemoglobin reduction is presentdecreased methemoglobin reduction is present

Inherited:Inherited: 1. Cytochrome b5 reductase deficiency: 1. Cytochrome b5 reductase deficiency: type I: limited to RBCtype I: limited to RBC type II: All cells (most die in infancy)type II: All cells (most die in infancy) 2. Hemoglobin M disease: mutation in either alpha 2. Hemoglobin M disease: mutation in either alpha

or beta globin moleculeor beta globin molecule Acquired: Acquired: More common, result from increased More common, result from increased

methemoglobin formation methemoglobin formation by various exogenous (most of the time by various exogenous (most of the time

pharmacologic) agents more than the rate of its pharmacologic) agents more than the rate of its reduction.reduction.

The Fugate Family“The Blue People of Troublesome Creek”

Agents implicated in Acquired Agents implicated in Acquired

MethemoglobinemiaMethemoglobinemia

Agents implicated in Acquired Methemoblobinemia

Amyl nitriteAniline derivativesButyl nitriteBismuth subnitriteDapsoneLidocaineBenzocaineMentholNaphthalenePhenytoinNTGNitrophenolNiprideNitritesNitratesPhenacetinPhenolsPyridiumQuinonesSilver nitrateSulfonamides

Benzocaine FormulationsBenzocaine Formulations

Benzocaine is available in spray form, Benzocaine is available in spray form, throat lozenges, and liquid and gel throat lozenges, and liquid and gel preparationspreparations

The spray form is prepared as 14% to 20%The spray form is prepared as 14% to 20% The average expulsion rate is 200 mg/secThe average expulsion rate is 200 mg/sec The average dose that The average dose that cancan produce produce

methemoglobinemia is>300 mg in adults methemoglobinemia is>300 mg in adults The package insert: “spray for ½ second, The package insert: “spray for ½ second,

may repeat as needed”may repeat as needed”

Risk FactorsRisk Factors Excessive dose Excessive dose Concurrent use of multiple oxidizing Concurrent use of multiple oxidizing

agentsagents Mucosal damage or inflammation are Mucosal damage or inflammation are

contributing factorscontributing factors Absorption is particularly rapid from the Absorption is particularly rapid from the

tracheobronchial tree, as it is technically tracheobronchial tree, as it is technically equivalent to IV administration equivalent to IV administration

Differences in the metabolism of Differences in the metabolism of benzocaine may explain the variability of benzocaine may explain the variability of benzocaine-induced methemoglobinemiabenzocaine-induced methemoglobinemia

High Risk PopulationsHigh Risk Populations

Patients with methemoglobin reductase Patients with methemoglobin reductase deficiency or G6PD deficiency deficiency or G6PD deficiency

Pediatric population and especially Pediatric population and especially neonates: due to low levels of functional neonates: due to low levels of functional NADP methemoglobin reductase NADP methemoglobin reductase

Elderly: NADP becomes less efficient Elderly: NADP becomes less efficient Impaired hepatic or renal functionImpaired hepatic or renal function Low Oxygen transport states: anemia, Low Oxygen transport states: anemia,

acidosis, low cardiac output state, acidosis, low cardiac output state, pulmonary disease pulmonary disease

Clinical PresentationClinical Presentation Onset of symptom is usually within 20 to 60 Onset of symptom is usually within 20 to 60

minutes of drug administrationminutes of drug administration The symptoms and signs of The symptoms and signs of

methemoglobinemia correlate to the amount methemoglobinemia correlate to the amount of abnormal hemoglobin presentof abnormal hemoglobin present

Usually, 5 g/dL (>30% of total hemoglobin) of Usually, 5 g/dL (>30% of total hemoglobin) of reduced hemoglobin (deoxyhemoglobin) reduced hemoglobin (deoxyhemoglobin) produces clinical cyanosis; but only 1.5 g/dL produces clinical cyanosis; but only 1.5 g/dL (>10%) of methemoglobin produces (>10%) of methemoglobin produces noticeable cyanosis due to the combined:noticeable cyanosis due to the combined:

1. Decrease in O2 carrying capacity 1. Decrease in O2 carrying capacity 2. shift in oxyhemoglobin dissociation curve 2. shift in oxyhemoglobin dissociation curve

to the left to the left

Methemoglobin

Symptoms and SignsSymptoms and Signs

15-20% Asymptomatic cyanosis

20-45%Headache, dyspnea, weakness,

dizziness, lethargy, syncope

45-60%Decrease level of

consciousness, metabolic acidosis, tachypnea

60-70%

Seizures, cardiac arrhythmias, homodynamic instability and shock

>70% Fatal

DiagnosisDiagnosis Diagnostic suspicion of methemoglobinemia is Diagnostic suspicion of methemoglobinemia is

based on clinical findings: generalized based on clinical findings: generalized cyanosis out of proportion to respiratory cyanosis out of proportion to respiratory status and normal PaO2, and doesn’t improve status and normal PaO2, and doesn’t improve with administration of O2with administration of O2

Arterial blood drawn for blood sampling is Arterial blood drawn for blood sampling is chocolate brown, blue, or black and fail to chocolate brown, blue, or black and fail to change color when exposed to air (unlike change color when exposed to air (unlike deoxyhemoglobin) or when a drop is dried on deoxyhemoglobin) or when a drop is dried on filter paperfilter paper

The “oxygen saturation gap”The “oxygen saturation gap” Cooximetry is the diagnostic test of choice Cooximetry is the diagnostic test of choice

The cyanosis is generalized, and doesn’t improve with 100% oxygen

The cyanosis has been referred to as “chocolate cyanosis”

The Oxygen Saturation The Oxygen Saturation GapGap

Refers to the difference between the Refers to the difference between the high O2 sat high O2 sat calculatedcalculated from routine from routine ABG analysis and the low O2 sat ABG analysis and the low O2 sat measuredmeasured by pulse oximetry by pulse oximetry

Methemoglobinemia should be Methemoglobinemia should be suspected when O2 Sat suspected when O2 Sat (ABG)(ABG) >O2 Sat >O2 Sat (pulse OX)(pulse OX)

The Routine ABG in The Routine ABG in MethemoglobinemiaMethemoglobinemia

The PaO2 usually is normal or The PaO2 usually is normal or inappropriately highinappropriately high

In routine ABG analysis O2 saturation In routine ABG analysis O2 saturation is is calculatedcalculated from PaO2 and pH, this from PaO2 and pH, this leads to falsely “normal” leads to falsely “normal” calculatedcalculated O2 sat on the ABG analysisO2 sat on the ABG analysis

Hence, the routine ABG by itself has Hence, the routine ABG by itself has no role in the diagnosis of no role in the diagnosis of methemoglobinemiamethemoglobinemia

Pulse OximetryPulse Oximetry It usually yields information based on the It usually yields information based on the

ratio of light absorbance of ratio of light absorbance of oxyhemoglobin (940 nm) and reduced oxyhemoglobin (940 nm) and reduced hemoglobin (660 nm)hemoglobin (660 nm)

Methemoglobin absorbs light equally at Methemoglobin absorbs light equally at both wavelengths (940 and 660), with both wavelengths (940 and 660), with pulse oximetry displaying a O2 Sat of pulse oximetry displaying a O2 Sat of 85%85%

Hence; the higher the methemoglobin Hence; the higher the methemoglobin concentration, the closer the O2 Sat to concentration, the closer the O2 Sat to 85%, regardless of patient status 85%, regardless of patient status

Multiple Wavelength Multiple Wavelength Spectrophotometry Spectrophotometry

(Cooximetry)(Cooximetry) Is the diagnostic test of choice for Is the diagnostic test of choice for

methemoglobinemiamethemoglobinemia It is based upon analysis of methemoglobin It is based upon analysis of methemoglobin

absorption spectra which has peak absorption spectra which has peak absorbance at 631 nmabsorbance at 631 nm

A fresh specimen should always be obtained A fresh specimen should always be obtained as the methemoglobin levels increase with as the methemoglobin levels increase with storagestorage

Hyperlipidemia interfere with the light Hyperlipidemia interfere with the light absorption and can cause falsely elevated absorption and can cause falsely elevated methemoglobinmethemoglobin

Treatment Treatment

Discontinue the offending agentDiscontinue the offending agent Most of the cases resolve within 24-Most of the cases resolve within 24-

36 hours after the clearing of the 36 hours after the clearing of the residual Benzocaineresidual Benzocaine

General supportive measures (O2, General supportive measures (O2, close observation) are appropriate close observation) are appropriate when methemoglobin level are when methemoglobin level are <30%<30%

TreatmentTreatment In more severe cases In more severe cases

(methemoglobin>30%) methylene (methemoglobin>30%) methylene blue in the dose of 1to 2 mg/kg of blue in the dose of 1to 2 mg/kg of 1% solution slow IV push over 5 1% solution slow IV push over 5 minutes is the preferred treatment. minutes is the preferred treatment.

Cyanosis resolve within 15-30 Cyanosis resolve within 15-30 minutesminutes

Marked reduction in the Marked reduction in the methemoglobin concentration methemoglobin concentration usually by 50% is seen within 30 to usually by 50% is seen within 30 to 60 minutes60 minutes

Methylene blue acts as a reducing Methylene blue acts as a reducing agent via the NADPH agent via the NADPH methemoglobin reductase pathway methemoglobin reductase pathway It converts ferric iron back to It converts ferric iron back to ferrous state, restoring the O2 ferrous state, restoring the O2 carrying capacity of hemoglobincarrying capacity of hemoglobin

TreatmentTreatment Administration can be repeated in 1 hour if Administration can be repeated in 1 hour if

symptoms do not resolvesymptoms do not resolve Methylene blue by itself has oxidizing Methylene blue by itself has oxidizing

properties at higher doses, with toxic effects properties at higher doses, with toxic effects appearing in doses >7 mg/kg (dyspnea, chest appearing in doses >7 mg/kg (dyspnea, chest pain, tremors, hemolysis)pain, tremors, hemolysis)

Hyperbaric O2 and exchange transfusion may Hyperbaric O2 and exchange transfusion may be used in: be used in:

1. Patients with G6PD deficiency who do not 1. Patients with G6PD deficiency who do not respond respond

to methylene blueto methylene blue 2. Severe cases (Methemoglobin level>70%) 2. Severe cases (Methemoglobin level>70%)

ConclusionsConclusions Benzocaine-induced methemoglobinemia Benzocaine-induced methemoglobinemia

is a rare but potentially fatal reaction is a rare but potentially fatal reaction that is imminently treatable if the that is imminently treatable if the diagnosis is not delayed diagnosis is not delayed

With the wide spread use of TEE, With the wide spread use of TEE, cardiologists need to be able to identify cardiologists need to be able to identify and treat this serious side effectand treat this serious side effect

Identifying high-risk patients, and the Identifying high-risk patients, and the judicious use of topical benzocaine is judicious use of topical benzocaine is crucial in prevention crucial in prevention

ConclusionsConclusions

The diagnosis is mainly clinical: with a The diagnosis is mainly clinical: with a chocolate-color cyanosis unresponsive to chocolate-color cyanosis unresponsive to O2 therapy, with a sudden drop of pulse O2 therapy, with a sudden drop of pulse oximeter reading to 85%oximeter reading to 85%

The saturation gap should alert the The saturation gap should alert the physician, and the diagnosis should be physician, and the diagnosis should be confirmed by cooxymetry confirmed by cooxymetry

Methylene blue should be readily Methylene blue should be readily available in areas where topical available in areas where topical anesthetics are frequently used anesthetics are frequently used

EndEnd

The Story of the BlueThe Story of the Blue

and the Blueand the Blue