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Methylene Blue by Intraosseous Infusion for Methemoglobinemia
CASE REPORT
Methylene Blue by Intraosseous Infusion for Methemoglobinemia From the Southern Poison Center, LeBonheur Children’s Medical Center, and The University of Tennessee, Memphis, Memphis, TN.
Martin I Herman, MD Peter A Chyka, PharmD Adrianne Y Butler, PharmD Sarah E Rieger, MD
Received for publication April 6, 1998. Revision received July 10, 1998. Accepted for publication August 4, 1998. Presented at The North American Congress of Clinical Toxicology, St. Louis, MO, September 1997. Address for reprints: Martin I Herman, MD, Southern Poison Center, 875 Monroe Avenue, Suite 104, Memphis, TN 38163. Copyright © 1999 by the American College of Emergency Physicians. 0196-0644/99/$8.00 +0 47/1/94615
Intraosseous administration of methylene blue may be an emergency alternative to intravascular administration. A 6-week-old female infant (3 kg) presented to the emergency department after a 1-week illness and appeared cyanotic and listless. Oxygen saturation by oximetry was 86% while the patient was receiving oxygen. Vital signs were blood pressure, 107/80 mm Hg; pulse, 190; respirations, 47; temperature, 39.0°C. A metabolic acidosis and a methemoglobin level of 29.3% were present. After several unsuccessful attempts to establish intravenous access, an intraosseous needle was placed in the infant’s left tibia. Methylene blue, 1 mg/kg, normal saline solution, and sodium bicarbonate were given intraosseously. The patient’s oxygen saturation rose to 98% to 100%, and her cyanosis improved. Three hours later, her methemoglobin level was 8.2%. The child recovered uneventfully and was sent home after 3 days. Intraosseous administration of standard intravenous doses of methylene blue rapidly terminated the effects of acquired methemoglobinemia. [Herman MI, Chyka PA, Butler AY, Rieger SE: Methylene blue by intraosseous infusion for methemoglobinemia. Ann Emerg Med January 1999;33:111-113.]
INTRODUCTION
Intraosseous infusion is accepted as an efficient way to establishemergency vascular access for the administration of fluids and medications when intravenous lines cannot be quickly established in acutely ill children.1,2 A variety of fluids and drugs have been given successfully by intraosseous infusion, including antidotes such as atropine, naloxone, and sodium bicarbonate.1,3 The intravenous antidote for acquired methemoglobinemia, methylene blue, has not previously been reported to have been administered intraosseously. We report a case of an infant with acquired methemoglobinemia who was treated successfully with methylene blue by intraosseous infusion.
JANUARY 1999
33:1
ANNALS OF EMERGENCY MEDICINE
1 1 1
INTRAOSSEOUS INFUSION FOR METHEMOGLOBINEMIA Herman et al
CASE REPORT
A 6-week-old female infant (3 kg) was brought to the emergency department after a 1-week illness involving vomiting and diarrhea. The child appeared ill, cyanotic, and listless. Pulse oximetry revealed an oxygen saturation of 86% while the child was receiving oxygen (10 L/min) by bag-valve mask. The vital signs were blood pressure, 107/80 mm Hg; pulse, 190; respirations, 47; temperature, 39.0°C. The only abnormal findings on physical examination were “steely blue” cyanosis, decreased capillary refill, and poor response to stimuli. Arterial blood gases were pH 7.21, partial pressure of carbon dioxide, 18 mm Hg; partial pressure of oxygen, 426 mm Hg; and bicarbonate concentration, 7 mmol/L with a base deficit of 18.7 mmol/L. Cooximetry yielded a methemoglobin level of 29.3%. After several unsuccessful attempts to establish intravenous access, an 18-gauge disposable intraosseous needle was placed in the infant’s left proximal anterior tibia. Methylene blue 1%, .3 mL (1 mg/kg), was slowly infused through the intraosseous line over 3 to 5 minutes (Figure). Eight minutes after the administration of methylene blue, the infant’s pulse oximetry reading was 98% to 100% and her cyanosis had resolved. A repeat methemoglobin determination 3 hours after the initial dose of methylene blue was 8.2%. At 3 hours into the hospital course, intravenous access was successfully established and the intraosseous infusion was discontinued. A second dose of methylene blue, .3 mL (1 mg/kg), was given intravenously at 7.8 hours after arrival at the hospital. Additional therapy included
DISCUSSION
Methemoglobinemia results when the iron moiety of hemoglobin is oxidized from the ferrous to the ferric state and impairs oxygen delivery to tissues. Symptoms depend on the degree of hypoxia, which is associated with the methemoglobin concentration. Infants may acquire methemoglobinemia during diarrheal illness, 4-7 from nitrates present in well water,4,7 and from a variety of oxidizing agents.4,7 Treatment includes intravenous administration of 1 to 2 mg/kg of methylene blue 1% solution infused over several minutes. This rapidly restores normal levels of methemoglobin of 1% to 2%.4,7 Methylene blue should be avoided in patients with known glucose-6phosphate dehydrogenase deficiency because of the potential development of hemolysis. 4,8 Doses of methylene blue in excess of 4 mg/kg can cause methemoglobinemia and hemolytic anemia.4
Oxygen saturation (%)
Figure.
Treatment of methemoglobinemia with methylene blue (arrow) by intraosseous (IO) and intravenous (IV) infusion in relation to oxygen saturation by pulse oximetry (circle) and blood methemoglobin level (square).
volume expansion with normal saline solution, 20 mL/kg, and correction of acidosis with sodium bicarbonate, 2 mEq/kg. The methemoglobin level was 4.4% when repeated at 18.3 hours after arrival at the ED. Three days later the child was sent home after an uneventful hospital stay. No apparent side effects were observed from the intraosseous administration of the methylene blue. The methemoglobinemia was thought to be caused by the well water used to prepare the child’s feedings, and it may have been exacerbated by a recent diarrheal illness.
Methemoglobin (%) 30
100
20 90 10 0
80 Oxygen
Room air
IO
IV
Methylene Blue
0
1 1 2
5
10 Time after admission (h)
15
ANNALS OF EMERGENCY MEDICINE
20
33:1 JANUARY 1999
INTRAOSSEOUS INFUSION FOR METHEMOGLOBINEMIA Herman et al
Treatment of methemoglobinemia requires adequate and prompt intravenous access. In our case, vascular access was difficult to establish, and an intraosseous needle was inserted. The intraosseous needle provided a means to administer methylene blue, which corrected this child’s methemoglobinemia. Although several complications are associated with the use of intraosseous needles, their occurrence is reported in fewer than 1% of patients. 1,3 Complications include improper placement, extravasation of fluids or drugs, compartment syndrome, skin necrosis, osteomyelitis, fat embolism, tibial fracture, and potential injury to the growth plate.1-3,9-12 Intraosseous infusion is used in children 6 years of age and younger,1,2 partly because young children have a lower marrow cavity fat content and lower risk of fat embolism than older children and adults.1,11 Standard intravenous doses of medications have been given intraosseously with success for resuscitation.1,3 In animal models, the serum concentrations or pharmacodynamic effects of drugs such as sodium bicarbonate,13 lidocaine,13 and phenobarbital14 have been found to be comparable after identical intraosseous and intravenous doses. Serum concentrations of drugs in a patient may be decreased after multiple attempts at placement of an intraosseous needle, compared with successful placement after 1 attempt.14 In our case, the standard intravenous dose of methylene blue4,8 was given empirically by intraosseous infusion and resulted in successful resolution of the child’s methemoglobinemia. Intraosseous administration of a standard intravenous dose of methylene blue rapidly and successfully terminated the effects of acquired methemoglobinemia.
9. Simmons CM, Johnson NE, Perkin RM, et al: Intraosseous extravasation complication reports. Ann Emerg Med 1994;23:363-366. 10. Rosovsky M, FitzPatrick M, Goldfarb CR, et al: Bilateral osteomyelitis due to intraosseous infusion: Case report and review of the English-language literature. Pediatr Radiol 1994;24:7273. 11. Orlowski JP, Julius CJ, Petras RE, et al: The safety of intraosseous infusions: Risks of fat and bone marrow emboli to the lungs. Ann Emerg Med 1989;18:1062-1067. 12. Wright R, Reynolds SL, Nachtsheim B: Compartment syndrome secondary to prolonged intraosseous infusion. Pediatr Emerg Care 1994;10:157-159. 13. Orlowski JP, Porembka DT, Gallagher JM, et al: Comparison study of intraosseous, central intravenous, and peripheral intravenous infusions of emergency drugs. Am J Dis Child 1990;144:112-117. 14. Brickman K, Rega P, Choo M, et al: Comparison of serum phenobarbital levels after single versus multiple attempts at intraosseous infusion. Ann Emerg Med 1990;19:31-33.
REFERENCES 1. Anonymous: Vascular access, in Chameides L, Hazinski MF (eds): Pediatric Advanced Life Support. Dallas: American Heart Association and American Academy of Pediatrics, 1997:5-1 to 5-17. 2. Advanced Trauma Life Support Course for Physicians, 5th ed. Chicago: American College of Surgeons, 1993:102-103,269. 3. Sawyer RW, Bodai BI, McCourt MM: The current status of intraosseous infusion. J Am Coll Surg 1994;179:353-360. 4. Curry S, Carlton MW: Hematologic consequences of poisoning, in Haddad LM, Shannon MW, Winchester JF (eds): Clinical Management of Poisoning and Drug Overdose, ed 3. Philadelphia: WB Saunders, 1998:223-235. 5. Pollack ES, Pollack CV: Incidence of subclinical methemoglobinemia in infants with diarrhea. Ann Emerg Med 1994;24:652-656. 6. Jolly BT, Monico EP, McDevitt B: Methemoglobinia in an infant: Case report and review of the literature. Pediatr Emerg Care 1995;11:294-297. 7. Dusdieker LB, Dungh CI: Nitrates and babies: A dangerous combination. Contemp Pediatr 1996;13:91-102. 8. Bolgiano EB, Barish RA: Use of new and established antidotes. Emerg Med Clin North Am 1994;12:317-334.
JANUARY 1999
33:1
ANNALS OF EMERGENCY MEDICINE
1 1 3
Methylene Blue by Intraosseous Infusion for Methemoglobinemia From the Southern Poison Center, LeBonheur Children’s Medical Center, and The University of Tennessee, Memphis, Memphis, TN.
Martin I Herman, MD Peter A Chyka, PharmD Adrianne Y Butler, PharmD Sarah E Rieger, MD
Received for publication April 6, 1998. Revision received July 10, 1998. Accepted for publication August 4, 1998. Presented at The North American Congress of Clinical Toxicology, St. Louis, MO, September 1997. Address for reprints: Martin I Herman, MD, Southern Poison Center, 875 Monroe Avenue, Suite 104, Memphis, TN 38163. Copyright © 1999 by the American College of Emergency Physicians. 0196-0644/99/$8.00 +0 47/1/94615
Intraosseous administration of methylene blue may be an emergency alternative to intravascular administration. A 6-week-old female infant (3 kg) presented to the emergency department after a 1-week illness and appeared cyanotic and listless. Oxygen saturation by oximetry was 86% while the patient was receiving oxygen. Vital signs were blood pressure, 107/80 mm Hg; pulse, 190; respirations, 47; temperature, 39.0°C. A metabolic acidosis and a methemoglobin level of 29.3% were present. After several unsuccessful attempts to establish intravenous access, an intraosseous needle was placed in the infant’s left tibia. Methylene blue, 1 mg/kg, normal saline solution, and sodium bicarbonate were given intraosseously. The patient’s oxygen saturation rose to 98% to 100%, and her cyanosis improved. Three hours later, her methemoglobin level was 8.2%. The child recovered uneventfully and was sent home after 3 days. Intraosseous administration of standard intravenous doses of methylene blue rapidly terminated the effects of acquired methemoglobinemia. [Herman MI, Chyka PA, Butler AY, Rieger SE: Methylene blue by intraosseous infusion for methemoglobinemia. Ann Emerg Med January 1999;33:111-113.]
INTRODUCTION
Intraosseous infusion is accepted as an efficient way to establishemergency vascular access for the administration of fluids and medications when intravenous lines cannot be quickly established in acutely ill children.1,2 A variety of fluids and drugs have been given successfully by intraosseous infusion, including antidotes such as atropine, naloxone, and sodium bicarbonate.1,3 The intravenous antidote for acquired methemoglobinemia, methylene blue, has not previously been reported to have been administered intraosseously. We report a case of an infant with acquired methemoglobinemia who was treated successfully with methylene blue by intraosseous infusion.
JANUARY 1999
33:1
ANNALS OF EMERGENCY MEDICINE
1 1 1
INTRAOSSEOUS INFUSION FOR METHEMOGLOBINEMIA Herman et al
CASE REPORT
A 6-week-old female infant (3 kg) was brought to the emergency department after a 1-week illness involving vomiting and diarrhea. The child appeared ill, cyanotic, and listless. Pulse oximetry revealed an oxygen saturation of 86% while the child was receiving oxygen (10 L/min) by bag-valve mask. The vital signs were blood pressure, 107/80 mm Hg; pulse, 190; respirations, 47; temperature, 39.0°C. The only abnormal findings on physical examination were “steely blue” cyanosis, decreased capillary refill, and poor response to stimuli. Arterial blood gases were pH 7.21, partial pressure of carbon dioxide, 18 mm Hg; partial pressure of oxygen, 426 mm Hg; and bicarbonate concentration, 7 mmol/L with a base deficit of 18.7 mmol/L. Cooximetry yielded a methemoglobin level of 29.3%. After several unsuccessful attempts to establish intravenous access, an 18-gauge disposable intraosseous needle was placed in the infant’s left proximal anterior tibia. Methylene blue 1%, .3 mL (1 mg/kg), was slowly infused through the intraosseous line over 3 to 5 minutes (Figure). Eight minutes after the administration of methylene blue, the infant’s pulse oximetry reading was 98% to 100% and her cyanosis had resolved. A repeat methemoglobin determination 3 hours after the initial dose of methylene blue was 8.2%. At 3 hours into the hospital course, intravenous access was successfully established and the intraosseous infusion was discontinued. A second dose of methylene blue, .3 mL (1 mg/kg), was given intravenously at 7.8 hours after arrival at the hospital. Additional therapy included
DISCUSSION
Methemoglobinemia results when the iron moiety of hemoglobin is oxidized from the ferrous to the ferric state and impairs oxygen delivery to tissues. Symptoms depend on the degree of hypoxia, which is associated with the methemoglobin concentration. Infants may acquire methemoglobinemia during diarrheal illness, 4-7 from nitrates present in well water,4,7 and from a variety of oxidizing agents.4,7 Treatment includes intravenous administration of 1 to 2 mg/kg of methylene blue 1% solution infused over several minutes. This rapidly restores normal levels of methemoglobin of 1% to 2%.4,7 Methylene blue should be avoided in patients with known glucose-6phosphate dehydrogenase deficiency because of the potential development of hemolysis. 4,8 Doses of methylene blue in excess of 4 mg/kg can cause methemoglobinemia and hemolytic anemia.4
Oxygen saturation (%)
Figure.
Treatment of methemoglobinemia with methylene blue (arrow) by intraosseous (IO) and intravenous (IV) infusion in relation to oxygen saturation by pulse oximetry (circle) and blood methemoglobin level (square).
volume expansion with normal saline solution, 20 mL/kg, and correction of acidosis with sodium bicarbonate, 2 mEq/kg. The methemoglobin level was 4.4% when repeated at 18.3 hours after arrival at the ED. Three days later the child was sent home after an uneventful hospital stay. No apparent side effects were observed from the intraosseous administration of the methylene blue. The methemoglobinemia was thought to be caused by the well water used to prepare the child’s feedings, and it may have been exacerbated by a recent diarrheal illness.
Methemoglobin (%) 30
100
20 90 10 0
80 Oxygen
Room air
IO
IV
Methylene Blue
0
1 1 2
5
10 Time after admission (h)
15
ANNALS OF EMERGENCY MEDICINE
20
33:1 JANUARY 1999
INTRAOSSEOUS INFUSION FOR METHEMOGLOBINEMIA Herman et al
Treatment of methemoglobinemia requires adequate and prompt intravenous access. In our case, vascular access was difficult to establish, and an intraosseous needle was inserted. The intraosseous needle provided a means to administer methylene blue, which corrected this child’s methemoglobinemia. Although several complications are associated with the use of intraosseous needles, their occurrence is reported in fewer than 1% of patients. 1,3 Complications include improper placement, extravasation of fluids or drugs, compartment syndrome, skin necrosis, osteomyelitis, fat embolism, tibial fracture, and potential injury to the growth plate.1-3,9-12 Intraosseous infusion is used in children 6 years of age and younger,1,2 partly because young children have a lower marrow cavity fat content and lower risk of fat embolism than older children and adults.1,11 Standard intravenous doses of medications have been given intraosseously with success for resuscitation.1,3 In animal models, the serum concentrations or pharmacodynamic effects of drugs such as sodium bicarbonate,13 lidocaine,13 and phenobarbital14 have been found to be comparable after identical intraosseous and intravenous doses. Serum concentrations of drugs in a patient may be decreased after multiple attempts at placement of an intraosseous needle, compared with successful placement after 1 attempt.14 In our case, the standard intravenous dose of methylene blue4,8 was given empirically by intraosseous infusion and resulted in successful resolution of the child’s methemoglobinemia. Intraosseous administration of a standard intravenous dose of methylene blue rapidly and successfully terminated the effects of acquired methemoglobinemia.
9. Simmons CM, Johnson NE, Perkin RM, et al: Intraosseous extravasation complication reports. Ann Emerg Med 1994;23:363-366. 10. Rosovsky M, FitzPatrick M, Goldfarb CR, et al: Bilateral osteomyelitis due to intraosseous infusion: Case report and review of the English-language literature. Pediatr Radiol 1994;24:7273. 11. Orlowski JP, Julius CJ, Petras RE, et al: The safety of intraosseous infusions: Risks of fat and bone marrow emboli to the lungs. Ann Emerg Med 1989;18:1062-1067. 12. Wright R, Reynolds SL, Nachtsheim B: Compartment syndrome secondary to prolonged intraosseous infusion. Pediatr Emerg Care 1994;10:157-159. 13. Orlowski JP, Porembka DT, Gallagher JM, et al: Comparison study of intraosseous, central intravenous, and peripheral intravenous infusions of emergency drugs. Am J Dis Child 1990;144:112-117. 14. Brickman K, Rega P, Choo M, et al: Comparison of serum phenobarbital levels after single versus multiple attempts at intraosseous infusion. Ann Emerg Med 1990;19:31-33.
REFERENCES 1. Anonymous: Vascular access, in Chameides L, Hazinski MF (eds): Pediatric Advanced Life Support. Dallas: American Heart Association and American Academy of Pediatrics, 1997:5-1 to 5-17. 2. Advanced Trauma Life Support Course for Physicians, 5th ed. Chicago: American College of Surgeons, 1993:102-103,269. 3. Sawyer RW, Bodai BI, McCourt MM: The current status of intraosseous infusion. J Am Coll Surg 1994;179:353-360. 4. Curry S, Carlton MW: Hematologic consequences of poisoning, in Haddad LM, Shannon MW, Winchester JF (eds): Clinical Management of Poisoning and Drug Overdose, ed 3. Philadelphia: WB Saunders, 1998:223-235. 5. Pollack ES, Pollack CV: Incidence of subclinical methemoglobinemia in infants with diarrhea. Ann Emerg Med 1994;24:652-656. 6. Jolly BT, Monico EP, McDevitt B: Methemoglobinia in an infant: Case report and review of the literature. Pediatr Emerg Care 1995;11:294-297. 7. Dusdieker LB, Dungh CI: Nitrates and babies: A dangerous combination. Contemp Pediatr 1996;13:91-102. 8. Bolgiano EB, Barish RA: Use of new and established antidotes. Emerg Med Clin North Am 1994;12:317-334.
JANUARY 1999
33:1
ANNALS OF EMERGENCY MEDICINE
1 1 3