preoperative complete blood count showed hemoglobin at 8.9 g / dl and hematocrit at 26.5% .
the electrocardiography , chest x - ray , and pulmonary function test showed no abnormal findings . after arriving at the or , the patient monitoring system ( polymount philips , usa ) was used to monitor the blood pressure , heart rate , pulse rate , and oxygen saturation by pulse oximeter .
she appeared stable , with a heart rate of 85 bpm , blood pressure 134/80 mmhg , and respiratory rate 14 bpm , but oxygen saturation by pulse oximeter was 85% on both fingers but normal on the anesthesiologist 's finger .
oxygen 6 l / min was administered by mask , and no abnormal breathing sounds were detected . in arterial blood gas analysis ,
however , the conjunctiva were pale ; her lips and fingernails were cyanosed ; and the oxygen saturation by pulse oximeter did not rise above 90% .
the patient 's guardian indicated that she had a 10-year history of grayish lips and fingernails .
although we considered delaying the surgery , the guardian wanted the surgery to proceed and the patient had the advanced gastric cancer accompanied by hemorrhage and perforation . before the anesthesia , a 20 g catheter was placed in the radial artery for continuous hemodynamic monitoring and arterial blood gas analysis .
after preoxygenation with oxygen at 6 l / min , lidocaine 20 mg , propofol 120 mg , and vecuronium 10 mg were administered , and manual ventilation was performed with oxygen at 6 l / min . however , the patient experienced severe cyanosis , and the oxygen saturation by pulse oximeter decreased to 79% .
after the tracheal intubation and controlled ventilation with oxygen at 3 l / min , the pulse oximeter increased to 83 - 85% . in arterial blood gas analysis after induction ,
the sampled blood was dark blackish brown , oxygen partial pressure was 224.7 mmhg , and oxygen saturation was 96.6% ( table 1 ) .
the difference between oxygen saturation by arterial blood gas analysis and oxygen saturation by pulse oximeter was presumably due to dyshemoglobin . for confirmation ,
arterial blood gas analysis and hemoglobin analysis using a co - oximeter ( abl520 , radiometer , cofenhagen , denmark ) was ordered for the department of laboratory medicine .
arterial blood gas analysis showed normal findings and hemoglobin analysis showed methemoglobin at 18.3% and oxyhemoglobin at 81.5% .
ascorbic acid 600 mg mixed in fluid was administered , and methylene blue 1 mg / kg was intravenously injected slowly over 3 minutes . the methemoglobin level reduced to 11.2% after the administration of ascorbic acid and reduced to 4.3% and then 2.3% after methylene administration .
anesthesia was sustained with oxygen at 3 l / min and enflurane 1.5 - 2.0 vol% .
after the surgery , the patient had a normal recovery of consciousness and spontaneous respiration , but was transferred to the intensive care unit ( icu ) . in the icu ,
one day after the surgery , we found that the patient had taken daspone 100 mg / day for 30 years for hansen 's disease without her family ever knowing .
after the surgery , methemoglobin in the blood went from 8.5% to 11.0% , but was untreated . from postoperative day 3 , it was treated under the diagnosis of adrenal apoplexy due to hypotension .
methemoglobin forms when hemoglobin 's fe ion oxides from ferrous ( fe ) to ferric ( fe ) . in healthy adults , a small amount of hemoglobin oxides to methemoglobin and
then it is rapidly converted back to hemoglobin such that methemoglobin levels remain below 1% .
this balance is maintained by the intracellular enzyme systems , nadh cytochrome - b5 methemoglobin reductase and nadph methemoglobin reductase .
methemoglobin can not reversibly bind with oxygen or carbon monoxide because of its additional cation , so it reduces the oxygen - carrying capacity in arterial blood .
it also causes a leftward shift of the oxygen dissociation curve , increasing the affinity of the hemoglobin for oxygen and reducing tissue oxygen supply .
symptoms of methemoglobinemia are primarily related to the level of methemoglobin but are also influenced by other factors , such as the total hemoglobin level and the cardiovascular status and the respiratory function .
usually , at methemoglobin levels below 15% , patients have no clinical symptoms if adequate hemoglobin levels and preserved cardiac output is sufficient
. however , when methemoglobin levels are 15 - 20% , blackbrown blood and cyanosis occur .
higher levels ( 20 - 45% ) cause headaches , somnolence , tachycardia , lethargy , and dizziness . when it is 45% or above , respiratory difficulty , acidemia , arrhythmia , heart failure , and seizures occur . when above 70% , there is a high risk of death .
methemoglobinemia can be caused congenitally , by certain foods , or by other unknown causes , but usually occurs when the patient is exposed to drugs or chemical substances that disturb the conversion of methemoglobin to hemoglobin and quicken the development of methemoglobin . when discovered in the perioperative period , it is usually due to the exposure of drugs or chemical substances such as : amyl nitrite , ethyl nitrite , sodium nitrite , silver nitrate , bismuth subnitrate , nitroglycerin , quinones , sulfonamide , sulfapyridine , sulfathiazole , aniline dye , acetanilid , aminobenzenes , aminophenol , benzocaine , prilocaine , and phenacetin .
the drugs used in anesthetic practice that cause methemoglobinemia are prilocaine , benzocaine , amyl nitrite , nitroglycerine , phenacetin , and sulfonamide .
dapsone is a sulfone antibiotic used for the treatment of hansen 's disease and other dermatologic diseases , as well as in immunosuppressed patients to prevent pneumocystitis carinii pneumonia or organ transplant patients , especially those intolerant to sulfonamide .
methemoglobinemia is a known side - effect of dapsone [ 4 - 6 ] and the patients of most cases had a history of dapsone - intake .
the patient here had a 30-year history of dapsone - intake , although this information was not obtained initially .
the plasma half - life varies from 10 to 80 hours and is dose - dependent .
the pulse oximeter uses 2 wavelengths , 660 nm and 990 nm , to calculate oxygen saturation because the absorbance difference between oxyhemoglobin and deoxyhemoglobin is maximized .
methemoglobin has the same absorbability as oxyhemoglobin and deoxygemoglobin so can affect oxygen saturation measurements by pulse oximeter .
low methemoglobin levels slight decrease oxygen saturation measurements to a limit of 85% , even with fatal methemoglobin levels .
arterial blood gas analysis calculates oxygen saturation based on arterial oxygen tension and the temperature and may not reflect actual oxygen saturation .
methemoglobinemia diagnosis includes cyanosis ; low arterial oxygen saturation that can not be explained by a problem in the respiratory system or cardiovascular system ; and when the normal oxygen partial pressure in the arterial blood gas analysis does not align with the oxygen saturation by the pulse oximeter .
oxygen carrying status is most accurately measured by analysis of all hemoglobin types with a co - oximeter .
congenital , chronic methemoglobinemia involves a family history or exposure to drugs and toxins , which could be captured in an accurate history . here , before anesthesia the patient showed cyanosis and low oxygen saturation on the pulse oximeter , which did not align with the arterial blood gas analysis .
however , the diagnosis of dyshemoglobins was delayed because of the patient refusal to share her medical history .
methemoglobin levels were 18.3% initially , and the patient had asymptomatic cyanosis and was hemodynamically stable , but she was given immediate treatment . despite adequate manual ventilation with oxygen at 6 l / min during anesthetic induction , the patient developed worsened cyanosis and showed decreased oxygen saturation by pulse oximeter to 79% .
the eldely patient had diabetes , hypertension , and anemia , potentially indicating ischemic heart disease or impairment in the oxygen - carrying capacity .
ascorbic acid and methylene blue treatment reduced methemoglobin levels to 11.2% , 4.3% , followed by maintenance of hemoglobin level with 2 u of packed red cells .
cyanosis and 85% oxygen saturation on pulse oximeter before anesthesia could indicate high methemoglobin levels .
despite adequate preoxygenation and manual ventilation with oxygen at 6 l / min anesthesia reduced oxygen saturation by pulse oximeter to 79% and the cyanosis worsened .
the anesthetics propofol , vecuronium , and enflurane are not oxidants that develop methemoglobin , although local anesthetics like prilocaine and benzocaine do , and it is uncertain that lidocaine is a oxidant .
after tracheal intubation and manual ventilation with oxygen at 6 l / min , the pulse oximeter went up to 84 - 85% and cyanosis decreased .
therefore , reduced oxygen saturation during anesthetic induction resulted from normal respiratory depression and not anesthetic drugs . in healthy patients , the slight respiratory depression and reduced arterial oxygen partial pressure caused respiratory depressants may be ignored , but in methemoglobinemia , they may cause seriously low oxygen saturation .
methemoglobinemia treatment is immediate intravenous administration of methylene blue ( 1 - 2 mg / kg ) and the removal of toxins or drugs that could cause it .
methylene blue acts as a cofactor of methemoglobin reductase and accelerates the enzymatic breakdown of methemoglobin .
higher levels ( 4 - 15 mg / kg / day ) can directly oxidize hemoglobin to methemoglobin and cause hemolytic anemia in glucose-6-phosphate dehydrogenase deficient patients .
methemoglobin levels above 30% should be treated , but methemoglobin levels below 15% may seem clinically insignificant .
however even when the methemoglobin level is low , treatment is recommended for patients with symptoms or underlying diseases with decreased oxygen - carrying capacity such cardiac disease , pulmonary disease , carbon monoxide intoxication , anemia , or acidosis .
life - threatening methemoglobinemia unresponsive to methylene blue may occasionally respond to ascorbic acid as well , although ascorbic acid works slowly .
other reported treatments are homogeneous transfusion , exchange transfusion , and hyperbaric oxygen treatment . in conclusion
the anesthesiologist should perform pulse oximeter and arterial blood gas analysis on patients with cyanosis .
when the two results do not align , or when the oxygen saturation by pulse oximeter does not align with the clinical manifestations , methemoglobinemia should be suspected .
the presence of dyshemoglobin should be confirmed by performing a hemoglobin analysis with a co - oximeter .
methemoglobinemia should be treated with methylene blue when necessary according to methemoglobin level , symptom , and underlying diseases .
 methemoglobinemia is an uncommon but potentially fatal disorder . 
 most cases have no adverse clinical consequence and require no treatment , but methemoglobinemia is often overlooked as a cause of low oxygen saturation , and often mistaken for the more common causes of hypoxia by anesthesiologists despite simple bedside tests that indicate the presence of this treatable abnormality . 
 we present a 68-year - old female patient who underwent gastrectomy for advanced gastric cancer with bleeding . in the preoperative period , 
 the patient showed cyanosis and oxygen saturation was 85% by pulse oximeter , but oxygen saturation by arterial blood gas analysis was 100% . 
 after tracheal intubation , the methemoglobin level was 18.3% . 
 ascorbic acid and methylene blue were administered . during preanesthetic evaluation , 
 the patient had not informed the anesthesiologist that she had been taking dapsone . 
Case Report
Discussion