Anesthesia for Children with Inborn Errors of Metabolism: Opening Up the Black Box

Many physicians may rarely – or even never – encounter a patient with inborn errors of metabolism (IEM), a group of disorders involving errors in the coding of enzymes, resulting in erroneous handling of various metabolic substrates. However, for the pediatric anesthesiologist, knowledge of these disorders is critically important, as 1 in 800 live births is affected by an IEM; the consequences of these disorders in the perioperative period can be catastrophic. Dr. Johnny Kenth of the Royal Manchester Children’s Hospital offered a thoughtfully organized review of the disorders, followed by evidence-based guidelines for perioperative management of this fragile cohort.

Disorders of Carbohydrate Metabolism

This includes disease such as galactosemia, glycogen storage diseases (of which there are over a dozen forms), congenital lactose intolerance, hereditary fructose intolerance, diabetes mellitus and scurvy. In every case, avoidance of catabolic states – that is, avoidance of hypoglycemia through minimization of fasting, is of critical importance, as these patients are unable to reliably maintain their blood glucose levels without consistent feeding. This can be achieved via glucose-enhanced infusion of intravenous fluids whilst still permitting desired GI emptying. Basic chemistries, LFTs and coagulation panels should be monitored closely, as these disorders predispose patients to kidney and/or liver failure (depending on the disorder), as well as coagulopathic states. EKG, TTE and cardiology consultation may be warranted, as accumulation of glycogen storage products can particularly impact heart muscle, leading to structural problems (such as HOCM) and arrhythmias. Myopathies and weakness can result in limited respiratory reserve, postoperative atelectasis and ineffective cough, predisposing these patients to delayed recovery and increased rate of infection. Moreover, many of these disorders can predispose to truncal obesity, further impinging on respiratory reserve. Anatomically, these patients can have troublesome airways, secondary to disease-related structural changes to the mouth (for example, macroglossia) and larynx. Care should be used when administering muscle relaxation to myopathic patients, as their response may be exaggerated and unpredictable.

Disorders of Amino Acid Metabolism

This group of disorders includes phenylketonuria, alkaptonuria, glutaric aciduria, homocystinuria and tyrosinuria. In each case, an error in amino acid handling leads to accumulation of toxic products, which over time, can have devastating manifestations. PKU is perhaps one of the more well-known in this group; an error in phenylalanine hydoxylase leads to mishandling of Phe conversion to tyrosine, resulting in an accumulation of phenylpyruvate. This can result in progressive mental retardation, seizures and other manifestations of brain damage.

Alkaptonuria is caused by an error in the handling of tyrosine, resulting in an accumulation of homogentisic acid; this can cause kidney stones, heart valve damage and osteoarthritis. In every case, anesthesia care begins with an avoidance of catabolic states, continuation of these patients’ protein restricted diets, and maintenance of nutritional supplementation (such as B12 and biotin) that may provide crucial co-enzymes. Since these patients are prone to metabolic acidosis, avoidance of fluids that may add o this acid load is crucial–care should be taken with the use of lactate Ringer’s solution, for example, as this can exacerbate the liver’s faulty management of pyruvate. Certain medications should be avoided, such as neuromuscular blockade requiring ester hydrolysis (cisatricurium and succinylcholine, for example) and NSAIDs derived from propionic acid (such as ibuprofen, naproxen and ketoprofen).

Disorders of Fatty Acid Oxidation and Mitochondrial Disorders

This group of disorders includes dehydrogenase deficiency (such as medium-chain acyl coenzyme A dehydrogenase deficiency, or MCADD), carnitine cycle defects, beta-oxidation defects, electron transfer defects, ketogenesis defects and mitochondrial disorders (such as myoclonus epilepsy with ragged red fibers, Leber’s optic neuropathy and myo-neurogenic gastrointestinal encephalopathy). Again, a major feature of the anesthetic management of these children includes the avoidance of catabolic states and thus, minimization of fasting. Analysis of laboratory values including basic chemistries and LFTs is again of great import, given the dramatic impact that can be had on these organ systems; like disorders of carbohydrate metabolism, cardiac involvement is also common and care of these patients should involve cardiology consultation. Interestingly, several anesthestic agents should be avoided all together, including most volatiles, propofol, barbiturates, benzodiazepines, and ketamine; clonidine, dexmedetomidine, desflurane and xenon appear to safe.

Urea cycle defects and lysosomal storage diseases

This group of disorders includes ornithine transcarbamylase deficiency, citrullinemia, arginiema, mucopolysaccharidoses (such as Hunter’s and Hurler’s disease), sphingolipidoses (such as Gaucher’s and Neiman-Picks’ disease), gangliosidoses (Tay-Sach’s). Many of the anesthetic-relevant manifestations of these diseases involve connective tissue; for example, these children can present with distorted epiglottis and larynx, as well as aberrant cervical spine growth, causing difficult airway conditions. These anatomical challenges can cause issues not just with airway management on induction, but also following emergence: these easily-obstructed airways can result in hypoxemia, negative pressure pulmonary edema, stridor, and cardiac arrest. Reintubation and/or tracheostomy should be early considerations for the struggling patient.

Ultimately, the first steps in successful management of patients with IEM requires awareness and recognition on the part of anesthesiologist: knowing what you could be up against is the key to anticipating catastrophe. A team-approach at a center well-equipped to manage complex pediatric patients is crucial, given the myriad of organ systems involved in children afflicted with these challenging disorders.

*Coverage of the Review Course Lecture, Anesthesia for Children with Inborn Errors of Metabolism: Opening Up the Black Box