Anesth Analg 2008; 107:648-650
© 2008 International Anesthesia Research Society
doi: 10.1213/ane.0b013e3181770fcc
GENERAL ARTICLE
Anesthetic Management of a Patient with 3-Methylcrotonyl-CoA Carboxylase Deficiency
Karen A. Robbins, MD, and
Elias N. León-ruiz, MD
From the Department of Anesthesiology and Perioperative Medicine, University Hospitals Case Medical Center, Cleveland, Ohio.
Address correspondence to Karen A. Robbins, MD, Children’s National Medical Center, 111 Michigan Ave NW, Suite W3.5-600, Washington, DC 20010-2970. Address e-mail to robbinska{at}gmail.com.
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Abstract
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Patients with inborn errors of metabolism require special considerations in perioperative care. In the following case report, we describe the successful management of a patient with 3-methylcrotonyl-CoA carboxylase deficiency, a deficit that causes a secondary carnitine deficiency and impaired β oxidation. Patients may have significant underlying cardiomyopathy, and are at risk for metabolic decompensation, acidosis, and hypoglycemia during periods of stress.
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Introduction
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Patients with inborn errors of metabolism may require special considerations in perioperative care. 3-Methylcrotonyl-CoA carboxylase deficiency (3-MCCD), previously a rare diagnosis, is now recognized with increasing frequency because of recent enhancements in newborn screening techniques.1,2 3-MCCD (Online Mendelian Inheritance in Man, OMIM #210200, 210210) causes secondary carnitine deficiency (Fig. 1) and impaired β oxidation.3 Patients may be profoundly carnitine deficient without adequate supplementation,3 and are at risk for severe metabolic decompensation, acidosis, and hypoglycemia during periods of prolonged fasting, illness, and acute stress.3–5 Cardiac and skeletal myopathy are predicted by the dependence of these tissues on fatty acid metabolism as a primary energy source, and compromised β oxidation may lead to exaggerated responses to medical interventions.6,7,8 A careful choice of anesthetics is necessary to minimize risks for carnitine-deficient patients, including cardiotoxicity, inhibition of mitochondrial acyl-carnitine transport, and further impairment of β oxidation.6–9 Here, we describe the first case report of successful anesthetic management for a patient with 3-MCCD.
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CASE REPORT
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An asymptomatic 30-yr-old woman with 3-MCCD underwent general anesthesia for a elective loop electrosurgical excision procedure for cervical dysplasia. The patient had a body mass index of 43 and a mallampati airway Class 3, was taking daily oral carnitine supplementation, and was otherwise healthy. Two years earlier she was diagnosed with 3-MCCD incidentally after an abnormal Ohio newborn screen was obtained from her child. The patient denied any history of symptoms referable to either 3-MCCD or cardiac compromise, including fatigue, muscle pain and weakness, decreased exercise tolerance, and a history of chest pain or palpitations. The preoperative electrocardiogram revealed T wave abnormality suggestive of anterior ischemia; however, this was unchanged compared with prior electrocardiogram examinations. A resting transthoracic echocardiogram was performed 2  yr prior, and revealed an overall systolic function at the lower limits of normality with an ejection fraction of 50%–55% with no regional wall motion abnormalities. The patient was premedicated IV with 2 mg midazolam and 100 µg fentanyl and, after establishing basic intraoperative monitoring, an IV induction was achieved with 100 mg lidocaine and 20 mg etomidate. A size 4 laryngeal mask airway was then inserted, which increased the patient’s arterial blood pressure to 175/100 mm Hg. This was treated successfully with 50 mg propofol IV. Anesthesia was maintained with sevoflurane 3.2% (dialed) in 1.5 L/min air and 1.5 L/min oxygen. The course of anesthesia was unremarkable and lasted for approximately 30 min. Emergence was rapid, and the patient recovered completely and was discharged to her home 2 h later.
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DISCUSSION
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3-MCCD, an autosomal recessive disorder of leucine catabolism, is now recognized as one of the most common organic acidurias, with a frequency of nearly 1 of 40,000.1,2 Along with an increased rate of diagnosis in newborns, many asymptomatic family members are being tested and identified.1 These patients, who may be otherwise healthy or have unrecognized clinical features, present unique management issues, as they are still at significant risk for decompensation when stressed.3,4 The decision to proceed with an elective case such as ours should consider a number of factors, including carnitine supplementation and patient compliance (carnitine levels should be obtained if clinically indicated), overall nutritional status (including fasting duration and glycemia), cardiovascular compromise, and comorbidity. We determined that, for our case, the patient had no other risk factors for secondary carnitine deficiency (malabsorbtion, cirrhosis, chronic renal failure, renal tubular acidosis, depakote use)10 and had adequate supplementation with daily oral carnitine dosing. Hypoglycemia was not apparent in our patient, but the prolonged period of fasting (15 h) would have made it advisable to monitor her blood glucose level.
One possible complication of 3-MCCD and carnitine deficiency is cardiomyopathy,11 which is predicted by dependence of cardiac muscle on β oxidation as a primary energy source. Although our patient denied symptoms of congestive heart failure or arrhythmia, her echocardiogram did reveal systolic function at the lower limits of normal. The rate of progression of carnitine deficiency cardiomyopathy is unknown in affected individuals, but we did not find any clinical evidence that the patient’s cardiac status had changed significantly since the time of the echocardiographic examination. We also did not believe that her overall cardiac risk was sufficient to warrant cancellation of the case. However, it is important to recognize the possible existence of some degree of underlying cardiomyopathy in patients with 3-MCCD, and to conduct a thorough evaluation before proceeding with these cases.
It is also important to recognize that carnitine-deficient patients may be particularly susceptible to stressors that overwhelm or inhibit mitochondrial metabolism,8 underscoring the need for a cautious selection of anesthetics. The effects of a standard induction dose of propofol in a patient taking adequate carnitine supplementation has not been studied, but we avoided propofol as an induction drug out of concern that it might further impair mitochondrial function by overwhelming the β oxidation pathway with a high lipid load. We chose to induce with etomidate based on its more favorable cardiac profile. Although the effects of this drug on cortisol levels were also a concern, we determined the intraoperative and postoperative stress of the surgical procedure to be rather negligible, and that a cardiac conservative approach was permissible. We did administered a small dose of propofol early in this case in response to hypertension after the laryngeal mask airway placement, but deemed the dose too small to produce additional inhibition of fatty acid metabolism. The fact that carnitine deficiency and propofol infusion syndrome involve similar derangements in the oxidative metabolism of fatty acids suggest a strong and perhaps absolute contraindication for propofol infusion in patients with 3-MCCD and other known mitochondrial disorders.7,8
Finally, although regional anesthesia was not used in our case, we wish to mention unique risks associated with bupivacaine and mitochondrial disorders. Several mechanisms have been proposed for the well-described phenomenon of bupivacaine-related cardiotoxicity, including inhibition of acylcarnitine exchange in cardiac mitochondria.6 Thus, inhibition of mitochondrial fatty acid transport in the case of carnitine-deficient patients may also lead to exaggerated cardiotoxicity. Seemingly safe doses of bupivacaine may provoke significant inhibition of myocardial respiration, and an accidental intravascular injection could precipitate arrhythmia or cardiovascular collapse.6,12 Furthermore, the accepted treatment of bupivacaine toxicity, a lipid solution,13 is contraindicated in carnitine-deficient patients for the reasons explained above. Given that both symptomatic and asymptomatic patients with 3-MCCD may have underlying cardiomyopathy of various degrees, the prudent selection of a local anesthetic is essential.
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Footnotes
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Accepted for publication March 20, 2008.
Reprint requests to Elias N. León-ruiz, MD, Department of Anesthesiology and Perioperative Medicine, University Hospitals Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106-5007.
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REFERENCES
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Abstract
Introduction
