ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Joseph W. Lewis, Jr
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lorelli, D. R.
Right arrow Articles by Lewis, J. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lorelli, D. R.
Right arrow Articles by Lewis, J. W., Jr
Related Collections
Right arrow Anesthesia

Ann Thorac Surg 2001;71:703-705
© 2001 The Society of Thoracic Surgeons

Case report

Drug-induced methemoglobinemia during thoracoscopic lung biopsy

David R. Lorelli, MDa, David E. Morris, MDa, Joseph W. Lewis, Jr, MDb

a Department of General Surgery, Henry Ford Hospital, Detroit, Michigan, USA
b Department of Thoracic Surgery, Henry Ford Hospital, Detroit, Michigan, USA

Accepted for publication March 24, 2000.

Address reprint requests to Dr Lewis, Department of Thoracic Surgery, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI 48202
e-mail: drjwlewis{at}aol.com


   Abstract
Top
 Abstract
Introduction
 Comment
 References
 
Acquired methemoglobinemia occurs rarely in clinical practice. We present a case of a 57-year-old man who developed severe drug-induced methemoglobinemia after exposure to benzocaine spray and lidocaine jelly during intubation for an elective thoracoscopic lung biopsy. Information regarding the classifications, pathophysiology, diagnosis, and treatment of this entity is reviewed.


   Introduction
Top
 Abstract
 Introduction
Comment
 References
 
Acquired methemoglobinemia is a rare but clinically important problem. It can occur in a number of different situations and mimic a multitude of other, more common, pathologic entities. As a result, our recent experience with acquired methemoglobinemia is reviewed in order to alert other physicians to the presentation, diagnosis, and treatment of this disorder.

A 57-year-old man with a history of rheumatoid arthritis, treated previously with steroids and gold salts, underwent evaluation for continuing dyspnea on exertion, cough, and recurrent episodes of bronchitis. Chest radiograph demonstrated a persistent interstitial pattern despite treatment with antibiotics and corticosteroids. An elective thoracoscopic lung biopsy for presumed bronchiolitis obliterans was planned. Shortly after using benzocaine spray and lidocaine jelly to facilitate an awake intubation, pulse oximeter measurements progressively declined to 65% with FiO2 of 1.00 and the patient became cyanotic. A chest radiograph revealed no pneumothorax and confirmed adequate endotracheal tube position. Electrocardiogram and transesophageal echocardiogram, respectively, revealed no evidence of myocardial ischemia or pulmonary embolus. Arterial blood gas measurements demonstrated a PaO2 of 681 mmHg, a SaO2 of 100%, a PCO2 of 35 mmHg, with pH of 7.38. Because of persistent cyanosis and an arterial blood sample that appeared dark brown in color, a methemoglobin level was obtained which revealed a level of 60% initially. Of those medications administered in the operating room, benzocaine spray and lidocaine jelly were the only known methemoglobin inducers.

Intravenous methylene blue (1 mg/kg) was administered, after which the subsequent methemoglobin level decreased to 34%. While in the operating room, one additional dose of methylene blue was administered and the patient was maintained on an FiO2 of 1.00 with sedation and paralysis. He was transported to the intensive care unit where over the next 3 hours his methemoglobin level continued to decline. He was extubated later that evening. The patient was discharged 2 days later in his normal state of health. An open lung biopsy performed uneventfully days later revealed a desquamative interstitial pneumonia-like pattern.


   Comment
Top
 Abstract
 Introduction
 Comment
References
 
Methemoglobinemia develops when the iron molecule in hemoglobin is oxidized to the ferric ion (Fe3+) from the normal reduced ferrous state (Fe2+). As a result of this oxidation, methemoglobin is incapable of binding and transporting oxygen [1, 2, 4]. Methemoglobinemia can be divided into three different categories: physiologic, congenital, and acquired.

Under normal physiologic conditions, approximately 1% of total hemoglobin is found in the oxidized form. This balance between oxidized and reduced forms is maintained by two different mechanisms. First, oxidizing molecules are reduced by reactions with compounds such as glutathione, ascorbic acid, sulfhydryl compounds, or by enzymes such as glutathione reductase and catalase; second, is by direct enzymatic reduction of methemoglobin to normal hemoglobin. The majority of this activity (95%) comes from nicotinamide adenine dinucleotide (NADH)-dependent methemoglobin reductase. The remainder (5%) is provided by nicotinamide adenine dinucleotide phosphate (NADPH)-dependent methemoglobin reductase. A cofactor of the NADPH-dependent enzyme is methylene blue which, when supplied, can result in a marked increase in activity for this enzyme [2].

Congenital forms of methemoglobinemia are very rare. They result from either a deficiency of NADH-dependent methemoglobin reductase or an abnormal hemoglobin state (Hgb M disease) [3, 4].

Acquired methemoglobinemia can be induced by a large number of drugs and chemicals which are systemically absorbed following ingestion, inhalation, or dermal exposure (Table 1). These compounds may be direct oxidants or have oxidizing metabolites or intermediaries. This oxidized state results in methemoglobin which cannot transport oxygen resulting in a leftward shift of the oxyhemoglobin dissociation curve. Functionally, this decreases oxygen delivery and hinders oxygen unloading from the remaining normal oxyhemoglobin at the tissue level.


View this table:
[in this window]
[in a new window]
  		Table 1. Common Drugs or Chemicals Known to Cause Acquired Methemoglobinemia

 
Clinical manifestations of methemoglobinemia depend on the percentage of oxidized hemoglobin. Concentrations of 10% to 15% may result in a dark or chocolate brown color to the blood along with cyanosis usually involving the trunk and proximal limbs. Levels between 20% to 45% have been associated with lethargy, dizziness, headache, and syncopal episodes. As levels approach 50% to 70%, seizures, arrhythmias, coma, hemodynamic instability, and death may result [5]. A presumptive diagnosis of methemoglobinemia can be established by examining the blood for a dark brown color. Also, arterial blood gas measurements will reveal a difference between PaO2 saturation and cooximeter measured percent oxygen saturation. This is a finding consistent with the existence of nonoxygen transporting hemoglobin derivatives such as methemoglobin, carboxyhemoglobin, and sulfhemoglobin. When suspicion exists for this disease, methemoglobin levels should be measured with a cooximeter.

Once diagnosed, treatment begins by stopping the administration of any drug known to induce methemoglobin, along with the administration of supplemental oxygen in order to maximize tissue oxygen delivery by the remaining functional hemoglobin. In severe cases, intubation and ventilation along with hemodynamic support may be necessary, as coma or circulatory collapse may develop. Specific treatment for methemoglobinemia involves administration of intravenous methylene blue, 1 to 2 mg/kg dose given over 5 minutes, with the total dose not to exceed 7 mg/kg [4, 5]. This will increase the activity of the NADPH-dependent enzyme allowing for a more rapid reduction of methemoglobin which would normally take about 24 to 72 hours. Patients should then be cautioned about the causative drug or evaluated for a congenital form of methemoglobinemia.

Methemoglobinemia has been reported in many clinical contexts. As a result, it is imperative that all physicians performing this, or any other type of procedure using local anesthetics, realize the possibility of such an untoward reaction. This unusual presentation shortly after intubation for a thoracic surgical procedure illustrates the importance of an awareness by surgeons and anesthesiologists for this entity, as many other processes may confound the diagnosis.


   References
Top
 Abstract
 Introduction
 Comment
 References
 

  1. Linares L.A., Peretz T.Y., Chin J. Methemoglobinemia induced by topical anesthetic (benzocaine). Radiother Oncol 1990;18:267-269.[Medline]
  2. Hall A.H. Systemic asphyxiants. In: Rippe J.M., Irwin R.S., Fink M.P., Cerra F.B., eds. Intensive care medicine. New York: Little, Brown and Company, 1996:1711-1714.
  3. Mansouri A., Lurie A.A. Concise review: methemoglobinemia. Am J Hematol 1993;42:7-12.[Medline]
  4. Jaffe E.R. Methaemoglobinemia. Clin Hematol 1981;10:99-122.
  5. Rodriguez L.F., Smolik L.M., Zbehlik A.J. Benzocaine-induced methemoglobinemia: report of a severe reaction and review of the literature. Ann Pharmacother 1994;28:643-648.[Abstract]



This article has been cited by other articles:


Home page
 PediatricsHome page
A. Dahshan and G. K. Donovan
Severe Methemoglobinemia Complicating Topical Benzocaine Use During Endoscopy in a Toddler: A Case Report and Review of the Literature
Pediatrics, April 1, 2006; 117(4): e806 - e809.
[Abstract] [Full Text] [PDF]

Home page
 ANN INTERN MEDHome page
C. Lawrence and M K. Abdrabbo
Angioedema as a Complication of Upper Endoscopy
Ann Intern Med, August 5, 2003; 139(3): W-62 - W-62.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Joseph W. Lewis, Jr
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lorelli, D. R.
Right arrow Articles by Lewis, J. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lorelli, D. R.
Right arrow Articles by Lewis, J. W., Jr
Related Collections
Right arrow Anesthesia

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS