1 / 27

Lab Rounds

Lab Rounds. Yael Moussadji Feb 12, 2009. Case. A previously healthy 3 y/o male (15kg) presented to the ED with perioral and nail bed cyanosis The morning prior he had been complaining of tooth pain and was treated with a topical local anesthetic

feo
Télécharger la présentation

Lab Rounds

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Lab Rounds Yael Moussadji Feb 12, 2009

  2. Case • A previously healthy 3 y/o male (15kg) presented to the ED with perioral and nail bed cyanosis • The morning prior he had been complaining of tooth pain and was treated with a topical local anesthetic • That morning, his mother had seen him swallow a small amount of topical anesthetic, and within 2 hours became “dusky” with clearly demonstrated cyanosis on the lips and nail beds • He has had no recent viral or diarrheal illnesses and no ill contacts

  3. Case • On examination, he had central and peripheral cyanosis, but no evidence of respiratory distress • He was playing quietly by himself in the room • Initial vital signs were HR 90, BP 100/50, RR 25, T 37.1, and SpO2 74% on R/A • A non-rebreather mask with 15L/min O2 was applied with no improvement in the child’s colour or oxygen saturation • As the nurse began to draw blood, she noted that the blood was dark brown in colour

  4. Ddx of Cyanosis • Cyanosis is most commonly caused by 2 mechanisms • An excess of deoxygenated hemoglobin • A significant amount of abnormal hemoglobin • With an abrupt onset of central and acral cyanosis in this previously healthy boy in the absence of significant respiratory distress, this is more likely to be due to a toxicologic or environmental cause

  5. Investigations • Mom pulls out a tube of topical anesthetic which is labeled 20% benzocaine gel • A blood gas is sent, and demonstrates the following • pH 7.33, PCO2 32, PaO2 400, HCO3 24 • Electrolytes are normal, no anion gap • SpO2 82%, MHb 48%

  6. Methemoglobinemia • Methemoglobin refers to the oxidation of ferrous iron (Fe++) to ferric iron (Fe+++) within the hemoglobin molecule • This reaction causes a leftward shift in the O2-Hb dissociation curve and impairs the ability of Hb to transport oxygen and CO2 leading to tissue hypoxemia and in severe cases, death • It commonly results from exposure to an oxidizing chemical, but may also arise from genetic, dietary, or even idiopathic etiologies

  7. Physiology • A number of reduction systems are in place to reduce iron from the ferric state to the ferrous state and maintain oxygen transport and delivery • In the presence of these reduction systems and under normal oxidative stress, RBCs are able to maintain a baseline MHb concentration of 0.5-1% by reconverting MHb to Hg at a maximal rate of about 15%/hr using first order kindetics • The cytochrome-b5-MHb reductase system is the predominant system, accounting for 95% of the daily MHb reduction

  8. Cytochrome MHb Reductase

  9. Other pathways • A second pathway uses NADPH and NADPH-dependent MHb reductase to reduce MHb • This pathway is dependent on the generation of NADPH through a process that involves G6PD • This is the conduit for the reduction of MHb by the administration of methylene blue

  10. Pathophysiology • The accumulation of excess MHb within RBCs overwhelms the baseline reduction rate and produces a conformation change to the Hb tetramer • This limits oxygen binding, and increases the binding affinity of the remaining ferrous iron • The resulting leftward shift in the oxygen-Hb dissociation curve and decreased oxygen carrying capacity produces a cellular hypoxia • Because oxidized Hb is incapable of carrying O2 and CO2, excess MHb causes cyanosis, impaired aerobic respiration, metabolic acidosis, and possibly death

  11. Etiology • Etiology can be thought of congenital or acquired • Acquired methemoglobinemia can be toxin induced, idiopathic (related to acidosis), or dietary

  12. Congenital • Results from one of 2 inherited pathways • An inhereted amino acid substitution at one of the binding sites on the Hb molecule creates an environment that favours the ferric state (autosomal dominant) • A second inherited deficiency is cytochrome b5 reductase reduces the ability of the RBC to reduce ferric iron (autosomal recessive) • These patients present very early in life with cyanosis

  13. Acquired • The most common cause of MHb is ingestion or skin exposure to an oxidizing agent • MHb is most common in children >6mo • Drugs themselves are usually not causative agents, but are metabolized to an oxidative free-radical • Agents commonly associated with methemoglobinemia • Benzocaine • Dapsone • Lidocaine • Nitrates • Nitrites (inhalent abuse) • Phenazopyridine • Primaquine • Prilocaine • Sulfonamides • (Chlorates)

  14. Benzocaine • Benzocaine is a member of the ester class of topical anesthetics and is found in numerous over the counter products marketed for the relief of teething, burns, hemorrhoids, sore throats • It is available in liquids, gels, sprays, lozenges, suppositories, creams, which typically contain between 5-20% benzocaine by volume • Benzocaine and other such drugs are all potent oxidative stressors because of their underlying amine constituent • Doses >15 mg/kg in infants are known to induce methemoglobinema

  15. Acquired • Other acquired causes include idiopathic MHb that is related to systemic acidosis • It can occur in young infants who develop severe metabolic acidosis as a results of sepsis, diarrhea, or dehydration • A third cause is related to well water nitrates (think about this in young infants who live in rural areas)

  16. Clinical Presentation • Generally, symptoms do not appear until MHb levels rise above 15-20% of the total Hb concentration, although some cyanotic skin discolouration may be present • At levels above between 20-30%, individuals may develop headaches, dizziness, lightheadedness, anxiety, sinus tachycardia, and tachypnea • At levels of 50-60%, myocardial ischemia, dysrhythmias, coma, seizures, and acidosis develop • At levels >70%, death usually results from severe cellular hypoxia

  17. Clinical Presentation • Small infants with MHb may present similarly to children with cyanotic congenital heart disease that fails to respond to supplemental oxygen • A distinguishing feature is an elevated PO2 despite clinical cyanosis, and a normal calculated oxygen saturation • Infants with sepsis may present in a similar fashion, but will respond to supplemental oxygen

  18. Investigations • The concentration of MHb, which is expressed as a % of total Hg, must be interpreted in the context of the blood Hg concentration • An anemic patient may have greater symptoms at a level of 20% than a non-anemic patient • Patients with underlying conditions that make them more susceptible to relative hypoxia (heart disease) may also cause them to manifest symptoms at lower levels

  19. Pulse Oximetry • The ratio of absorbance of two wavelengths, or the relative difference in light absorption between oxyHb and deoxyHg, reflects the percentage of Hb that is oxygenated at any given time • MHb will absorb light equally at both wavelengths • At a MHb of 100%, the ratio is 1.0, and the pulseoximeter reads 85% oxygen saturation • At lower levels of MHb the oxygen saturation will read slightly lower, but once MHb levels reach 30-35%, the light absorbance reaches a plateau and the pulse oximetry reading stabilizes at 82-86% • Therefore, significant levels of MHb will result in only mild to moderate oxygen desaturation

  20. ABG • The ABG is also limited in MHb because the oxygen saturation is derived from a nomogram and the PO2 • This conversion relies on the assumption that normal Hg is present • The presence of dyshemoglobins (MHb, COHg) will therefore result in falsely elevated oxygen saturations on the arterial blood gas analysis • If there is no access to co-oximetry, a saturation gap between the oxygen saturation obtained by pulse-oximetry and that obtained by ABG suggests the presence of abnormal hemoglobin

  21. Co-oximetry • The lab method of choice and will confirm the diagnosis of MHb • A spectrophotometer that measures light absorbance at 4 different wavelengths, which corresponds to the characteristics of deoxy-Hb, oxy-Hb, CO-Hg, and hemoglobin, using a specific peak absorbance to characterize MHb • These machines actually measure oxygen saturation instead of calculating it

  22. Treatment • After an exposure to an oxidizing agent, the actionable treatment level is considered to be approximately 20% if symptomatic or 30% if asymptomatic • Patients who are compromised due to underlying illness may need to be treated at lower levels • The treatment of choice is methylene blue, which is provided as a 1% solution (10mg/ml) • The dose is 1-2 mg/kg infused intravenously over 3-5 minutes, and may be repeated at 1 mg/kg if symptoms and levels do not resolve after 30 minutes • Methylene blue is excreted by the kidneys, resulting in blue-green discolouration of urine

  23. Complications • Complications have been reported in patients with G6PD deficiency and infants • Patients with G6PD deficiency may not respond to treatment because they can’t produce sufficient NADPH to reduce methylene blue to leukomethylene blue; they may also develop a paradoxically worsening MHb and hemolytic anemia because methylene blue, if not reduced, is an oxidant • This effect can be seen in the administration of large doses (>4mg/kg) as well, which has occurred in infants

  24. Other therapies • Supportive care • Removal of oxidative stressor • Dextrose (major source of NADH in the RBC is the catabolism of sugar through glycolysis) • NAC is being studied (electron donor)

  25. Case • The diagnosis was suggested by cyanosis that did not improve with supplemental oxygen, and exposure to an oxidizing agent • The gross appearance of his blood as a chocolate brown colour that did not change when exposed to oxygen was also suggestive of MHb • The patient was treated with 15 mg of methylene blue, based on a MHb level of 48%, which resulted in a dramatic improvement of his colour and oxygen saturation • A MHb level drawn before discharge was 1.7%

  26. Conclusion • Think of methemoglobinemia is patients who present with cyanosis with an appropriate exposure history (lots of oxidative toxins!) • Remember this in your approach to the cyanotic infant • Lack of response to supplemental oxygen and chocolate coloured blood that does not turn red on exposure to air is highly suggestive • Easily diagnosed with Co-oximetry • Treat with methylene blue 1-2 mg/kg if levels >20%

More Related