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Malignant ventricular dysrhythmias in a patient with isovaleric acidemia receiving general and local anesthesia for suction lipectomy
ELSEVIER
Case Reports Malignant Ventricular Dysrhythmias in a Patient with Isovaleric Acidemia Receiving General and Local Anesthesia for Suction Lipectomy Guy L. Weinberg, MD, * Charles E. Laurito, MD,? Peter Geldner, MD,1 Bernard H. Pygon, MD,* Barbara K Burton, MD§ Department
of Anesthesiology,
We report the occurrence of severe ventricular arrhythmias in a with isovalerk acidemia during general anesthesia for suction lipectomy. The timing of events and character of the ECG changes are most consistent with bupivacaine toxicity after subcutaneous injection of tumescence solution containing this local anesthetic. The patient had previously documented camitine deficiency, a condition which, we speculate, may lower the threshold for bupiwacaine induced cardiotoxicity. We review clinical considerations in isovaleric acidemia and conclude that the use of bupivacaine in these patients probably should be avoided. 0 199’7 by Elsevier Science Inc.
patient
Keywords: Acidemia, bupivacaine;
carnitine;
*&sistant Professor
isovaleric; arrhythmias; lipectomy.
of Anesthesiology,
University
of Illinois
College
of Anesthesiology,
University
of Illinois
College
of Medicine tAssociate Professor of Medicine
$Attending Physician, Department Medical Center, Chicago SProfessor of Pediatric College of Medicine
of Plastic
and Medical
Surgery,
Genetics,
Michael
University
Reese
of Illinois
Address correspondence to Dr. Weinberg at the Department of Anesthesiology, m/c 515, University of Illinois Hospital, 1740 West Taylor St., Chicago, IL 60612, USA. Received for publication April for publication July 21, 199’7.
11, 1997; revised
Journal 9:668-670, of Clinical Anesthesia 0 1997 by Elsevier Science Inc. 655 Avenue of the Americas, New York,
manuscript
1997 NY 10010
accepted
University of Illinois College of Medicine,
Chicago, IL
Introduction Isovaleric acidemia (IVA) is an autosomal recessive disease of leucine catabolism characterized by intermittent episodes of metabolic acidosis.’ It can present in either a neonatal or a late-onset form. Neonates typically present with failure to thrive, and both forms suffer bouts of vomiting, lethargy, metabolic acidosis, bone marrow depression, and a typical body odor of “sweaty feet” during periods of catabolic stress, such as infection.” Cardiac disease is not common, and perianesthetic complications have not been reported in isovaleric acidemia. We describe an intraoperative episode of severe ventricular dysrhythmias in an otherwise asymptomatic adolescent with late-onset isovaleric acidemia, who had received a small dose of subcutaneous bupivacaine.
Case Report A 16 year-old, 60 kg female with a history of late-onset isovaleric acidemia was scheduled for bilateral axillary liposuction. According to the patient, she was in excellent health except for one episode of nausea, vomiting, and lethargy eight years earlier, which led to her diagnosis. Her medical history was otherwise negative, and she stated that her symptoms were well controlled with oral glycine and carnitine therapy. On the morning of the procedure, routine monitors were applied and general anesthesia was induced with fentanyl, thiopental sodium, and vecuronium; an endotracheal tube was placed uneventfully, and 0952~8180/97,‘$17.00 PI1 SO952-8180(97)00187-6
Dysrhythmias
the patient was maintained on oxygen (0s)) nitrous oxide (N,O) , and desflurane. Three hundred mL of a modified Klein’s tumescent solution, a mixture of 0.0075% bupivacaine and epinephrine, 1:1,000,000, in lactated Ringer’s solution, were injected subcutaneously by the surgeon in the right axilla producing a pronounced, localized skin swelling. The total subcutaneous dose was relatively small and consisted of only 22 mg of bupivacaine and 300 mcg of epinephrine. Four minutes later, while the pulse oximeter and end-tidal CO, devices indicated normal readings, the patient’s electrocardiogram (EGG) changed from a normal sinus rhythm at 80 beats per minute (bpm) to a sinus rhythm of 40 bpm, to a junctional bradycardia and then to a wide complex ventricular dysrhythmia at 20 bpm. After these ECG changes, her blood pressure (BP) decreased from 130/70 mmHg to 60/40 mmHg. Emergency treatment consisted of the immediate cessation of inhaled anesthetic drugs, administration of 100% O,, and intravenous (IV) ephedrine 15 mg. The ECG then indicated a ventricular tachycardia at 160 bpm. Her end-tidal CO, concentration fell from 35 mmHg to 18 mmHg, and her heart rate (HR) was barely palpable. Lidocaine 100 mg and epinephrine 100 mcg were administered intravenously. The ECG converted to a sinus tachycardia of 150 bpm, and the Dynamap blood pressure monitor (Critikon, Tampa, FL) recorded a blood pressure of 120/80 mmHg. Although the entire episode of ECG and BP abnormalities lasted only 5 minutes, the procedure was aborted. The effects of muscle relaxant were reversed with neostigmine. The patient awoke, responded to commands, moved all extremities, and her trachea was extubated. The patient’s postoperative ECG showed a normal sinus rhythm but was noteworthy for the new onset of a prolonged QT interval. An echocardiogram showed mild left ventricular dysfunction. Her urinary toxicology screen was negative; a serum carnitine level performed the following day revealed a plasma free carnitine level of 32 FM. Values less than 20 FM are considered indicative of systemic carnitine deliciency. Although the information had not been available to the anesthesiologists, six weeks prior to this anesthetic the patient’s plasma free carnitine level at the time of the procedure was severely reduced at 7.8 ~.LM. A follow-up ECG taken one week later showed a normal QT interval, Discussion Isovaleric acidemia results from deficiency in isovalerylCoA dehydrogenase activity, a key enzyme in the catabolism of leucine, a branched-chain amino acid.3 Cytosolic transamination and mitochondrial decarboxylation of leucine produce isovalerylCoA. IsovalerylCoA dehydrogenase then catalyzes the first of four sequential oxidative reactions leading to acetoacetate, acetylCoA, and mevalonic acid. Deficiency in isovalerylCoA dehydrogenase causes accumulation of isovaleric acid and many of its metabolic derivatives, including isovalerylglycine and isovalerylcarnitine, which are nontoxic and excreted in the urine. Clinically significant isovaleric acidemia and metabolic acidosis generally occur in isovaleric acidemia
and
isoualtic
acidemia:
Weinberg
et al.
only during periods of accelerated protein catabolism.4 Systemic carnitine depletion is common in isovaleric acidemia because carnitine, trapped in the form of isovalerycarnitine, is chronically excreted in the urine. Patients with isovaleric acidemia are about equally divided between those with the neonatal form and those with the late onset form. Symptoms in both forms of isovaleric acidemia result from metabolic ketoacidosis. In the neonatal period, these symptoms include failure to thrive, vomiting, lethargy, myoclonus or seizures, hyperammonemia, marrow depression, hypothermia, and developmental delay. Patients surviving the neonatal form develop a clinical picture identical to the chronic, late onset form, which generally does not affect longevity. Symptoms in this form typically decrease in frequency with age, and may also include vomiting, lethargy, weakness, and marrow suppression, as well as diarrhea, dehydration, and alopecia. The classic body odor of “sweaty feet” during episodes is seen in both forms of the disease. Acute therapy of metabolic acidosis in isovaleric acidemia includes glucose and bicarbonate infusion, as well as administration of glycine and carnitine. Glycine and carnitine trap isovaleric acid as their corresponding acyl derivatives, which are water soluble and excreted in the urine.5-’ Chronic treatment combines dietary protein restriction with glycine and carnitine supplementation.‘,” Treatment with carnitine has the additional benefit of repleting carnitine stores.rO~‘r The exact etiology of our patient’s intraoperative arrhythmia is unknown. However, two metabolic sequelae of isovaleric acidemia: elevated intracellular isovalerylcarnitine and systemic carnitine depletion, could each theoretically lower the threshold for cardiac dysrhythmias in the presence of bupivacaine. Acylcarnitines are highly arrhythmogenic and systemic carnitine depletion is associated with cardiomyopathy.‘2,13 Although carnitine depletion is a recognized feature of isovaleric acidemia, cardiac disease is not reported in isovaleric acidemia. Our patient was apparently healthy and compliant with her glycine and carnitine regimen; the lack of symptoms and the normal serum carnitine level are consistent with well-controlled isovaleric acidemia. However, a low-serum carnitine concentration months before the operation suggests prior systemic carnitine depletion. The normal serum value drawn the day following the event does not, in itself, exclude a low tissue carnitine level, (personal communication, Peggy Borum, University of Florida, Gainesville, FL). The surgeon performing the case used a preoperative, subcutaneous injection of large volumes of a crystalloid solution containing both local anesthetic and epinephrine. Such tumescence solutions are thought to facilitate liposuction, as well as reduce bleeding and perioperative pain.14 A typical m’1x t m-e contains lidocaine 0.1% with epinephrine 1:1,000,000 and lidocaine doses of 30 mg/kg. Peak serum local anesthetic concentrations are usually achieved several hours after injection and are typically in the 1 to 3 microgram per mL range.15 Tumescent solutions are considered by the surgical community to be safe; J. Gin.
Anesth.,
vol. 9, December
1997
669
Case Reports
however, concerns about toxicity have recently been raised.16s1’ Tumescent solutions containing bupivacaine are favored by many surgeons. However, our patient received 300 ml of only 0.0075% bupivacaine and epinephrine 1:1,000,000. The total subcutaneous dose of bupivacaine was only 22 mg, or less than 0.4 mg/kg, which is far below a cardiotoxic dose. However, the timing of events suggests a possible correlation between injection of this small amount of bupivacaine in the tumescent solution in a patient with a carnitine deficiency. The progressive conduction blockade followed by bradycardia is consistent with bupivacaine toxicity. In summary, we report an intraoperative episode of ventricular dysrhythmias in a patient with adult-onset isovaleric acidemia. These patients may be more susceptible to the toxic effects of bupivacaine given the carnitine deficiency associated with the genetic defect. We suspect that intravascular absorption of the small dose of bupivaCaine (22 mg) led to acute bupivacaine toxicity as manifested by initial ECG changes followed by vital sign changes. In this patient population, the use of tumescence solutions containing even dilute preparations of bupivaCaine can deliver cardiotoxic doses of the local anesthetic and should, therefore, be avoided.
References 1. Tanaka K Isovaleric acidemia: personal history, clinical survey and study of the molecular basis. Prog Clin BiolRes 1990;321:27390. 2. Spirer 2, Swirsky-Fein S, Zakut V, et al: Acute neonatal isovaleric acidemia. A report of two cases. Isr J Med Sci 1975;11:1005-10. 3. Rhead WJ, Tanaka K Demonstration of a specific mitochondrial isovalery-CoA dehydrogenase deficiency in fibroblasts from patients with isovaleric acidemia. Pm Natl Acad Sci USA 1980;77:580-3.
670
J. Clin. Anesth.,
vol. 9, December
1997
4. Millington DS, Roe CR, Maltby DA, Inoue F: Endogenous catabolism is the major source of toxic metabolites in isovaleric acidemia. JPediatr 1987;110:56-60. 5. Cohn RM, Yudkoff M, Rothman R, Segal S: Isovaleric acidemia: use of glycine therapy in neonates. NEnglJMed 1978;299:996-9. 6. Krieger I, Tanaka K: Therapeutic effects of glycine in isovaleric acidemia. Pediatr Res 1976;10:25-9. 7. Naglak M, Salvo R, Madsen K, Dembure P, Elsas L: The treatment of isovaleric acidemia with glycine supplement, Pediatr Res 1988; 24:9-13. 8. Berry GT, Yudkoff M, Segal S: Isovaleric acidemia: medical and neurodevelopmental effects of long-term therapy. JPediatr 1988; 113(1 Pt 1):58-64. 9. de Sousa C, Chalmers RA, Stacey TE, Tracey BM, Weaver CM, Bradley D: The response to Lcarnitine and glycine therapy in isovaleric acidaemia. Eur JPediatr 1986;144:451-6. 10. Mayatepek E, Kurczynski TW, Hoppel CL: Long-term L-carnitine treatment in isovaleric acidemia. Pediatr Neural 1991;7:137-40. 11. Roe CR, Millington DS, Maltby DA, Kahler SG, Bohan TP: L-carnitine therapy in isovaleric acidemia. J C&n Invest 1984;74: 2290-5. 12. Corr PB, Yamada KA: Selected metabolic alterations in the ischemic heart and their contributions to arrhythmogenesis. Hm 1995;20:156-68. 13. Winter SC, Srabo-Aczel S, Curry CJ, Hutchinson HT, Hogue R, Shug A: Plasma carnitine deficiency. Clinical observations in 51 pediatric patients. AmJDis Child 1987;141:660-5. 14. Klein JA: Tumescent technique for local anesthesia improves safety in large-volume liposuction. Plast Reconstr Swg 1993;92: 1085-100. 15. Samdal F, Amland PF, Bugge JF: Plasma lidocaine levels during suction-assisted lipectomy using large doses of dilute lidocaine with epinephrine. Plast Reconstr Surg 1994;93:1217-23. 16. Klein JA: The tumescent technique. Anesthesia and modified liposuction technique. Dermatol Clin 1990;8:425-37. 17. Fodor PB: Wetting solutions in aspirative lipoplasty: a plea for safety in liposuction. Aesthetic Plast kg 1995;19:379-80.
Case Reports Malignant Ventricular Dysrhythmias in a Patient with Isovaleric Acidemia Receiving General and Local Anesthesia for Suction Lipectomy Guy L. Weinberg, MD, * Charles E. Laurito, MD,? Peter Geldner, MD,1 Bernard H. Pygon, MD,* Barbara K Burton, MD§ Department
of Anesthesiology,
We report the occurrence of severe ventricular arrhythmias in a with isovalerk acidemia during general anesthesia for suction lipectomy. The timing of events and character of the ECG changes are most consistent with bupivacaine toxicity after subcutaneous injection of tumescence solution containing this local anesthetic. The patient had previously documented camitine deficiency, a condition which, we speculate, may lower the threshold for bupiwacaine induced cardiotoxicity. We review clinical considerations in isovaleric acidemia and conclude that the use of bupivacaine in these patients probably should be avoided. 0 199’7 by Elsevier Science Inc.
patient
Keywords: Acidemia, bupivacaine;
carnitine;
*&sistant Professor
isovaleric; arrhythmias; lipectomy.
of Anesthesiology,
University
of Illinois
College
of Anesthesiology,
University
of Illinois
College
of Medicine tAssociate Professor of Medicine
$Attending Physician, Department Medical Center, Chicago SProfessor of Pediatric College of Medicine
of Plastic
and Medical
Surgery,
Genetics,
Michael
University
Reese
of Illinois
Address correspondence to Dr. Weinberg at the Department of Anesthesiology, m/c 515, University of Illinois Hospital, 1740 West Taylor St., Chicago, IL 60612, USA. Received for publication April for publication July 21, 199’7.
11, 1997; revised
Journal 9:668-670, of Clinical Anesthesia 0 1997 by Elsevier Science Inc. 655 Avenue of the Americas, New York,
manuscript
1997 NY 10010
accepted
University of Illinois College of Medicine,
Chicago, IL
Introduction Isovaleric acidemia (IVA) is an autosomal recessive disease of leucine catabolism characterized by intermittent episodes of metabolic acidosis.’ It can present in either a neonatal or a late-onset form. Neonates typically present with failure to thrive, and both forms suffer bouts of vomiting, lethargy, metabolic acidosis, bone marrow depression, and a typical body odor of “sweaty feet” during periods of catabolic stress, such as infection.” Cardiac disease is not common, and perianesthetic complications have not been reported in isovaleric acidemia. We describe an intraoperative episode of severe ventricular dysrhythmias in an otherwise asymptomatic adolescent with late-onset isovaleric acidemia, who had received a small dose of subcutaneous bupivacaine.
Case Report A 16 year-old, 60 kg female with a history of late-onset isovaleric acidemia was scheduled for bilateral axillary liposuction. According to the patient, she was in excellent health except for one episode of nausea, vomiting, and lethargy eight years earlier, which led to her diagnosis. Her medical history was otherwise negative, and she stated that her symptoms were well controlled with oral glycine and carnitine therapy. On the morning of the procedure, routine monitors were applied and general anesthesia was induced with fentanyl, thiopental sodium, and vecuronium; an endotracheal tube was placed uneventfully, and 0952~8180/97,‘$17.00 PI1 SO952-8180(97)00187-6
Dysrhythmias
the patient was maintained on oxygen (0s)) nitrous oxide (N,O) , and desflurane. Three hundred mL of a modified Klein’s tumescent solution, a mixture of 0.0075% bupivacaine and epinephrine, 1:1,000,000, in lactated Ringer’s solution, were injected subcutaneously by the surgeon in the right axilla producing a pronounced, localized skin swelling. The total subcutaneous dose was relatively small and consisted of only 22 mg of bupivacaine and 300 mcg of epinephrine. Four minutes later, while the pulse oximeter and end-tidal CO, devices indicated normal readings, the patient’s electrocardiogram (EGG) changed from a normal sinus rhythm at 80 beats per minute (bpm) to a sinus rhythm of 40 bpm, to a junctional bradycardia and then to a wide complex ventricular dysrhythmia at 20 bpm. After these ECG changes, her blood pressure (BP) decreased from 130/70 mmHg to 60/40 mmHg. Emergency treatment consisted of the immediate cessation of inhaled anesthetic drugs, administration of 100% O,, and intravenous (IV) ephedrine 15 mg. The ECG then indicated a ventricular tachycardia at 160 bpm. Her end-tidal CO, concentration fell from 35 mmHg to 18 mmHg, and her heart rate (HR) was barely palpable. Lidocaine 100 mg and epinephrine 100 mcg were administered intravenously. The ECG converted to a sinus tachycardia of 150 bpm, and the Dynamap blood pressure monitor (Critikon, Tampa, FL) recorded a blood pressure of 120/80 mmHg. Although the entire episode of ECG and BP abnormalities lasted only 5 minutes, the procedure was aborted. The effects of muscle relaxant were reversed with neostigmine. The patient awoke, responded to commands, moved all extremities, and her trachea was extubated. The patient’s postoperative ECG showed a normal sinus rhythm but was noteworthy for the new onset of a prolonged QT interval. An echocardiogram showed mild left ventricular dysfunction. Her urinary toxicology screen was negative; a serum carnitine level performed the following day revealed a plasma free carnitine level of 32 FM. Values less than 20 FM are considered indicative of systemic carnitine deliciency. Although the information had not been available to the anesthesiologists, six weeks prior to this anesthetic the patient’s plasma free carnitine level at the time of the procedure was severely reduced at 7.8 ~.LM. A follow-up ECG taken one week later showed a normal QT interval, Discussion Isovaleric acidemia results from deficiency in isovalerylCoA dehydrogenase activity, a key enzyme in the catabolism of leucine, a branched-chain amino acid.3 Cytosolic transamination and mitochondrial decarboxylation of leucine produce isovalerylCoA. IsovalerylCoA dehydrogenase then catalyzes the first of four sequential oxidative reactions leading to acetoacetate, acetylCoA, and mevalonic acid. Deficiency in isovalerylCoA dehydrogenase causes accumulation of isovaleric acid and many of its metabolic derivatives, including isovalerylglycine and isovalerylcarnitine, which are nontoxic and excreted in the urine. Clinically significant isovaleric acidemia and metabolic acidosis generally occur in isovaleric acidemia
and
isoualtic
acidemia:
Weinberg
et al.
only during periods of accelerated protein catabolism.4 Systemic carnitine depletion is common in isovaleric acidemia because carnitine, trapped in the form of isovalerycarnitine, is chronically excreted in the urine. Patients with isovaleric acidemia are about equally divided between those with the neonatal form and those with the late onset form. Symptoms in both forms of isovaleric acidemia result from metabolic ketoacidosis. In the neonatal period, these symptoms include failure to thrive, vomiting, lethargy, myoclonus or seizures, hyperammonemia, marrow depression, hypothermia, and developmental delay. Patients surviving the neonatal form develop a clinical picture identical to the chronic, late onset form, which generally does not affect longevity. Symptoms in this form typically decrease in frequency with age, and may also include vomiting, lethargy, weakness, and marrow suppression, as well as diarrhea, dehydration, and alopecia. The classic body odor of “sweaty feet” during episodes is seen in both forms of the disease. Acute therapy of metabolic acidosis in isovaleric acidemia includes glucose and bicarbonate infusion, as well as administration of glycine and carnitine. Glycine and carnitine trap isovaleric acid as their corresponding acyl derivatives, which are water soluble and excreted in the urine.5-’ Chronic treatment combines dietary protein restriction with glycine and carnitine supplementation.‘,” Treatment with carnitine has the additional benefit of repleting carnitine stores.rO~‘r The exact etiology of our patient’s intraoperative arrhythmia is unknown. However, two metabolic sequelae of isovaleric acidemia: elevated intracellular isovalerylcarnitine and systemic carnitine depletion, could each theoretically lower the threshold for cardiac dysrhythmias in the presence of bupivacaine. Acylcarnitines are highly arrhythmogenic and systemic carnitine depletion is associated with cardiomyopathy.‘2,13 Although carnitine depletion is a recognized feature of isovaleric acidemia, cardiac disease is not reported in isovaleric acidemia. Our patient was apparently healthy and compliant with her glycine and carnitine regimen; the lack of symptoms and the normal serum carnitine level are consistent with well-controlled isovaleric acidemia. However, a low-serum carnitine concentration months before the operation suggests prior systemic carnitine depletion. The normal serum value drawn the day following the event does not, in itself, exclude a low tissue carnitine level, (personal communication, Peggy Borum, University of Florida, Gainesville, FL). The surgeon performing the case used a preoperative, subcutaneous injection of large volumes of a crystalloid solution containing both local anesthetic and epinephrine. Such tumescence solutions are thought to facilitate liposuction, as well as reduce bleeding and perioperative pain.14 A typical m’1x t m-e contains lidocaine 0.1% with epinephrine 1:1,000,000 and lidocaine doses of 30 mg/kg. Peak serum local anesthetic concentrations are usually achieved several hours after injection and are typically in the 1 to 3 microgram per mL range.15 Tumescent solutions are considered by the surgical community to be safe; J. Gin.
Anesth.,
vol. 9, December
1997
669
Case Reports
however, concerns about toxicity have recently been raised.16s1’ Tumescent solutions containing bupivacaine are favored by many surgeons. However, our patient received 300 ml of only 0.0075% bupivacaine and epinephrine 1:1,000,000. The total subcutaneous dose of bupivacaine was only 22 mg, or less than 0.4 mg/kg, which is far below a cardiotoxic dose. However, the timing of events suggests a possible correlation between injection of this small amount of bupivacaine in the tumescent solution in a patient with a carnitine deficiency. The progressive conduction blockade followed by bradycardia is consistent with bupivacaine toxicity. In summary, we report an intraoperative episode of ventricular dysrhythmias in a patient with adult-onset isovaleric acidemia. These patients may be more susceptible to the toxic effects of bupivacaine given the carnitine deficiency associated with the genetic defect. We suspect that intravascular absorption of the small dose of bupivaCaine (22 mg) led to acute bupivacaine toxicity as manifested by initial ECG changes followed by vital sign changes. In this patient population, the use of tumescence solutions containing even dilute preparations of bupivaCaine can deliver cardiotoxic doses of the local anesthetic and should, therefore, be avoided.
References 1. Tanaka K Isovaleric acidemia: personal history, clinical survey and study of the molecular basis. Prog Clin BiolRes 1990;321:27390. 2. Spirer 2, Swirsky-Fein S, Zakut V, et al: Acute neonatal isovaleric acidemia. A report of two cases. Isr J Med Sci 1975;11:1005-10. 3. Rhead WJ, Tanaka K Demonstration of a specific mitochondrial isovalery-CoA dehydrogenase deficiency in fibroblasts from patients with isovaleric acidemia. Pm Natl Acad Sci USA 1980;77:580-3.
670
J. Clin. Anesth.,
vol. 9, December
1997
4. Millington DS, Roe CR, Maltby DA, Inoue F: Endogenous catabolism is the major source of toxic metabolites in isovaleric acidemia. JPediatr 1987;110:56-60. 5. Cohn RM, Yudkoff M, Rothman R, Segal S: Isovaleric acidemia: use of glycine therapy in neonates. NEnglJMed 1978;299:996-9. 6. Krieger I, Tanaka K: Therapeutic effects of glycine in isovaleric acidemia. Pediatr Res 1976;10:25-9. 7. Naglak M, Salvo R, Madsen K, Dembure P, Elsas L: The treatment of isovaleric acidemia with glycine supplement, Pediatr Res 1988; 24:9-13. 8. Berry GT, Yudkoff M, Segal S: Isovaleric acidemia: medical and neurodevelopmental effects of long-term therapy. JPediatr 1988; 113(1 Pt 1):58-64. 9. de Sousa C, Chalmers RA, Stacey TE, Tracey BM, Weaver CM, Bradley D: The response to Lcarnitine and glycine therapy in isovaleric acidaemia. Eur JPediatr 1986;144:451-6. 10. Mayatepek E, Kurczynski TW, Hoppel CL: Long-term L-carnitine treatment in isovaleric acidemia. Pediatr Neural 1991;7:137-40. 11. Roe CR, Millington DS, Maltby DA, Kahler SG, Bohan TP: L-carnitine therapy in isovaleric acidemia. J C&n Invest 1984;74: 2290-5. 12. Corr PB, Yamada KA: Selected metabolic alterations in the ischemic heart and their contributions to arrhythmogenesis. Hm 1995;20:156-68. 13. Winter SC, Srabo-Aczel S, Curry CJ, Hutchinson HT, Hogue R, Shug A: Plasma carnitine deficiency. Clinical observations in 51 pediatric patients. AmJDis Child 1987;141:660-5. 14. Klein JA: Tumescent technique for local anesthesia improves safety in large-volume liposuction. Plast Reconstr Swg 1993;92: 1085-100. 15. Samdal F, Amland PF, Bugge JF: Plasma lidocaine levels during suction-assisted lipectomy using large doses of dilute lidocaine with epinephrine. Plast Reconstr Surg 1994;93:1217-23. 16. Klein JA: The tumescent technique. Anesthesia and modified liposuction technique. Dermatol Clin 1990;8:425-37. 17. Fodor PB: Wetting solutions in aspirative lipoplasty: a plea for safety in liposuction. Aesthetic Plast kg 1995;19:379-80.