Page 1749 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

1218 PART 11: Special Problems in Critical Care

Li levels of >4.0 mEq/L in acute ingestion and >2.5 mEq/L in acute- TABLE 124-24 Selected Drugs/Toxins Associated With Acquired
on-chronic or chronic toxicity are significant levels and should lead to Methemoglobinemia
consideration of HD. HD is preferred to peritoneal dialysis because of
greater clearance. 303,311,312 Rebound increase of serum levels often occurs Acetanilid
several hours after dialysis; this phenomenon is mostly attributable to Amyl nitrite
slow extracellular transfer of intracellular lithium, although delayed Butyl nitrite
313
absorption from slow-release preparations may also be contributory.
314
Prolonged dialysis (8-12 hours) with a large surface area dialyzer is gen- Bromates
erally performed initially, with repetition as needed for levels in excess Aniline dyes
of 1.0 at 6 to 8 hours after treatment. Alternatively, there are advocates Benzocaine
for the use of continuous arteriovenous or venovenous hemofiltration/
hemodialysis to attain both dialytic clearance of extracellular Li and Bupivacaine
effective mobilization and removal of intracellular stores, 93,94 but these Chlorates
strategies may not be superior to standard HD. Acute HD followed by a Chloroquine
period of continuous venovenous hemodialysis to prevent rebound is a Dapsone
potentially useful combination.
■ METHEMOGLOBINEMIA Flutamide
Herbicides
Unlike reduced (Fe ) hemoglobin, oxidized (Fe ) hemoglobin (called Isobutyl nitrite
2+
3+
methemoglobin) is unable to release oxygen effectively to tissue beds. In Isosorbide dinitrate
health, a small amount of methemoglobin is formed by autooxidation of
circulating red blood cells continuously exposed to high concentrations Lidocaine
of oxygen. Reduced cytochrome b5 reacts with circulating methemo- Loxosceles gaucho venom
globin to restore hemoglobin and oxidized cytochrome b5. The red cell Methyl nitrite
enzyme NADH-cytochrome b5 reductase (methemoglobin reductase) is
responsible for regenerating reduced cytochrome b5, thereby ensuring Metoclopramide
insignificant concentrations of methemoglobin in circulating blood. 249,315 Nitric oxide
Hereditary methemoglobinemia develops when circulating methe- Nitroethane
moglobin cannot be reduced (eg, hemoglobin M) or there is a defi-
ciency in red cell cytochrome b5 reductase. These hereditary conditions Nitrobenzene
are generally of little clinical significance and usually do not require Nitroglycerin
treatment-acquired methemoglobinemia, which can be life threatening, Nitroprusside
occurs in the setting of oxidant drugs or toxin exposures (Table 124-24).
Physiologically, acquired methemoglobinemia occurs when the rate Pesticides
of ferric (Fe ) iron formation exceeds RBC rate of reduction through Petrol octane booster
3+
pathways discussed above. Many of these drugs, such as commonly used Phenacetin
analgesics, sulfonamides, sulfones, and local anesthetics, are derivatives Phenazopyridine
of aniline. These were originally called “blue oil” and can result in blue
people (those with methemoglobinemia). Aniline drugs, particularly Potassium ferricyanide
316
if taken in combination, are the most common cause of methemoglo- Prilocaine
binemia today. 316 Primaquine
Methemoglobinemia decreases oxyhemoglobin saturation and blood-
carrying capacity in a way that is analogous to carbon monoxide Pyridium Plus
poisoning. Not only does 50% methemoglobinemia effectively decrease Silver nitrate
hemoglobin concentration by half, methemoglobinemia also shifts the Sodium chlorite
oxyhemoglobin dissociation curve to the left, thereby interfering with
off-loading of oxygen in peripheral tissues. In mild methemoglobinemia Sodium nitrite
(<15% of the total hemoglobin), patients generally remain asymptom- Sulfonamides
atic despite examination evidence of cyanosis. One possible exception
is the patient with coronary artery disease, who may develop acute
coronary syndrome from this functional anemia. Higher methemoglo- contaminated clothing, washing of contaminated skin, and AC, depend-
bin concentrations result in dyspnea, headache, and weakness. Severe ing on the nature of the intoxication. Methylene blue, a dye capable of
methemoglobinemia (>60%) causes confusion, seizures, and death. reversing drug- or toxin-induced methemoglobinemia by increasing
Laboratory confirmation of elevated methemoglobin is available by conversion of methemoglobin to hemoglobin, should be considered
cooximetry, which directly measures oxygen and methemoglobin satu- in symptomatic patients with methemoglobin levels greater than 20%
rations. Of note, the antidote methylene blue (see below) falsely elevates or in asymptomatic patients with levels greater than 30%. A dose of
320
methemoglobin levels by cooximetry (a dose of 2 mg/kg methylene blue 1 to 2 mg/kg (0.1-0.2 mL/kg of a 1% solution) IV administered over
gives a falsely elevated methemoglobin level of 15%). Pulse oximetry 5 minutes generally results in a significant reduction in methemoglobin
is unreliable in methemoglobinemia. Because of alterations of pulse level within 30 to 60 minutes. A repeat dose of methylene blue may be
oximeter light absorption, oximetry may report an oxygen saturation of given after 60 minutes if needed. Additional doses may be required in
approximately 85% regardless of the actual value. Pulse oximetry may patients who have taken a long-acting oxidant drug such as dapsone;
249
be falsely high in patients with methemoglobinemia and falsely low after however, higher doses of methylene blue may paradoxically increase
methylene blue. 317,318 Another clue is the finding of chocolate-colored oxidant stress and methemoglobinemia. Contraindications to methylene
venous blood. 319 blue include G6PD deficiency (where methylene blue may trigger hemo-
Treatment of methemoglobinemia starts with supportive measures lytic anemia), renal failure (because the antidote is renally excreted),
and removal of the inciting drug or toxin. This may involve removal of and reversal of nitrite-induced methemoglobinemia during treatment

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