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4206 Litman-05.qxd 10/20/03 1:02 PM Page 1 5 RONALD S. LITMAN, D.O.
MARY C. THEROUX, M.D.
Cerebral Palsy
Respiratory system dysfunction usually parallels the Seizure Disorders
overall severity of the disease. Bulbar motor dysfunction Neuromuscular Diseases
causes a loss of normal airway protective mecha- nisms (cough, gag, etc.) and leads to chronic pulmonary aspiration, recurrent pneumonia, development of reac- tive airway disease, and parenchymal lung damage.
Consequently, children with severe CP will often exhibit Neurologic and neuromuscular disorders represent a a reduced functional residual capacity and lower than substantial percentage of pediatric coexisting disease, normal oxygen saturation. Bulbar dysfunction also and are associated with the need for a variety of sur- causes gastroesophageal symptoms that include gastroe- gical procedures during childhood. Cerebral palsy and sophageal reflux and an inability to swallow oropharyn- seizure disorders are very common in the pediatric pop- geal secretions. Gastrostomy tubes are often placed ulation, and thus anesthesiologists should be familiar during infancy to optimize nutritional status.
with their clinical characteristics and the pharmacologic Infants born prematurely may develop areas of brain agents used for their treatment. Although less common, ischemia secondary to cerebral hemorrhages in the early myopathies are associated with significant morbidity in newborn period.The area of infarction is termed “periven- children, and are noteworthy because of their associa- tricular leukomalacia” (white matter atrophy surround- tion with malignant hyperthermia and the potentially ing the ventricles) and is associated with development catastrophic hyperkalemic response to administration of of varying degrees of limb spasticity. Chronic absence of motor input results in progressive development of limbcontractures during childhood that worsen with age.
Baclofen, a gamma amino butyric acid (GABA) ago- CEREBRAL PALSY
nist, reduces pain associated with muscle spasms andslows development of contractures. Most children Cerebral palsy (CP) is often defined as a static motor receive it orally; however, intrathecal administration is encephalopathy. It encompasses a collection of motor possible for severe cases. Side-effects of baclofen include system disorders caused by a perinatal or early child- urinary retention and leg weakness, which usually abate hood neurological insult (Table 5-1).The incidence of CP when the dose is reduced. Abrupt withdrawal from oral in the United States is approximately 0.7 per 1000 live or intrathecal baclofen may cause seizures, hallucina- births and is rising. The contribution of very low birth- tions, disorientation, and dyskinesias. Overdose of weight infants to this population of children is signifi- baclofen is associated with depressed consciousness and cant: approximately 52,000 very low birthweight infants (<1500 g) are born annually. These infants make up more Botulinum toxin is also used to treat spasticity associ- than 25% of the children diagnosed with CP.
ated with CP. While the child is sedated, it is injected into Children with CP exhibit a wide variety of clinical man- contracted muscles and produces a functional denerva- ifestations that range from mild (e.g., slight lower-extremity tion of the muscle by preventing release of acetylcholine spasticity and normal cognitive function) to severe (e.g., from the presynaptic motor end-plate. This results in a spastic quadriplegia and profound mental retardation).
temporary reduction in muscle tone that may last for 4206 Litman-05.qxd 10/20/03 1:02 PM Page 2 PEDIATRIC ANESTHESIA: THE REQUISITES IN ANESTHESIOLOGY months.There are no significant side-effects from its use children with CP. Increased sensitivity to narcotics is or known interactions of botulinum toxin with anes- present in all but mild forms of cerebral palsy. Doses should be reduced, and greater vigilance at the time of Seizures are present in about 30% of patients with extubation is necessary to ensure the child’s ability to cerebral palsy. Anticonvulsants should be continued until maintain a patent upper airway. Hypothermia is a com- the morning of surgery and reinstituted as quickly as mon intraoperative problem in children with CP.
possible during the postoperative period.When it is not Impaired temperature regulation is caused by hypothala- feasible to continue oral or gastrostomy anticonvulsant mic dysfunction and the patient’s absence of muscle and administration, rectal (e.g., phenytoin, valproic acid, and carbamazepine) and intravenous (e.g., phenytoin, val- Postoperative regional analgesia may benefit children proic acid, and phenobarbital) options are possible. If the with CP who have difficulty communicating the severity surgical procedure causes significant blood loss, anticon- of their pain. Addition of epidural clonidine may help vulsant levels should be checked postoperatively, and reduce postoperative lower-limb spasticity. Oral diazepam doses should be adjusted to reestablish optimal levels.
0.2–0.3 mg /kg is used as an adjuvant to help alleviate Children with CP are often subjected to numerous surgical interventions during childhood. Orthopedic pro-cedures are the most common and include scoliosisrepair, and a variety of limb procedures to improve range SEIZURE DISORDERS
of motion and decrease progression of contractures.
Dorsal rhizotomy may be required to control painful Seizures are clinical manifestations of a variety of dis- lower limb spasticity. Nissen fundoplication is performed orders. Febrile seizures represent the most common type to control chronic gastroesophageal reflux and may of seizure disorder in the pediatric population (5%).
include a feeding gastrostomy.This is now performed by Idiopathic epilepsy, which is primarily seen in older chil- dren, is much less common, with an estimated incidence Preoperative assessment includes defining and opti- of approximately 0.6% of the population. Trauma, mizing all systemic medical illnesses. Concurrent upper hypoxia, and infection are the primary causes of seizures respiratory infections are poorly tolerated and exacer- in infants. Additional causes of seizures in children bate preexisting respiratory disease. Preoperative anxiol- include metabolic disease, hypoglycemia, electrolyte and ysis should be administered to children who are not metabolic abnormalities, toxic ingestions, and congenital cognitively impaired. Some children with CP are prone or developmental defects. However, in up to 50% of to upper airway obstruction when consciousness is seizure disorders, the etiology remains unknown.
depressed and should be closely monitored after the The currently accepted international classification of administration of the premedication. Administration of epileptic seizures divides these disorders into two broad an anticholinergic agent may decrease pooling of categories: partial and generalized (Box 5-1). Partial seizures are those in which the initial clinical and elec- There are no special considerations when choosing troencephalographic (EEG) changes indicate activation an agent for induction or maintenance of general anes- of a system of neurons limited to part of one cerebral thesia. If a gastrostomy tube is present, the stomach hemisphere. When consciousness is not impaired, is it should be evacuated prior to induction of general anes- labeled a simple partial seizure and indicates a unilateral thesia. Because of malformation of facial structures, mask cerebral event. When consciousness is impaired, it is ventilation may be difficult, but endotracheal intubation called a complex partial seizure and indicates a bilateral should be straightforward. Presence of gastroesophageal cerebral event. Partial seizures can consist of a variety of reflux and increased oropharyngeal secretions may manifestations that includes motor, sensory, autonomic, encourage the anesthesiologist to rapidly secure the air- or psychic phenomena.With partial seizures, there is usu- way using an intravenous induction agent. Children with ally no specific postictal state. Partial seizures can also cerebral palsy demonstrate increased sensitivity to suc- exhibit progression to generalized seizure activity.
cinylcholine but do not exhibit excessive potassium There are four basic types of generalized seizures: release after its use. Nevertheless, succinylcholine should • Absence seizures are also called “petit mal” seizures.
be used only to treat life-threatening airway emergen- They consist of staring spells during which the cies. Nondepolarizing muscle relaxants are less potent patient is not responsive, and last usually only a few and have a relatively shorter duration of action in children with CP. This may be related to chronic anticon- • Myoclonic seizures consist of brief twitching muscle activity that is uncoordinated.There are two types of Sevoflurane and halothane are relatively more potent myoclonic seizures: epileptic are those that originate (i.e., lower minimum alveolar concentration; MAC) in from cortical or subcortical tissues; nonepileptic 4206 Litman-05.qxd 10/20/03 1:02 PM Page 3 myoclonus originates from the brainstem or spinal anticonvulsant medications. The precise mechanism of cord and is due to loss of cortical inhibition or this phenomenon has not been elucidated. However, impaired function of spinal interneurons.
this resistance is not as prominent for those neuro- • Tonic–clonic seizures are those with which most muscular blockers that are metabolized in the plasma people are familiar.They consist of an initial tonic (i.e., atracurium, mivacurium), so it may be related to a contraction phase, during which it is common for pharmacokinetic effect based in the liver. There is also patients to become apneic and cyanotic from the some data and clinical experience indicating that anti- tonic rigidity of the thoracic cavity.This is followed convulsants may cause some resistance to opioids.
by the clonic, repetitive twitching phase, where Although definitive data are lacking, it does not appear breathing resumes but can be shallow and irregular.
that general anesthesia impacts the subsequent fre- • Atonic seizures are characterized by a state of quency or severity of seizures postoperatively.
Infantile spasms (West syndrome) consist of the triad of unique “salaam-like” seizure movements, arrest of psy- NEUROMUSCULAR DISEASES
chomotor development, and a characteristic EEG patterncalled “hypsarrhythmia.” The onset peaks at between Neuromuscular diseases can be broadly divided into 4 and 7 months of age and almost always occurs before disorders of the muscle, and disorders of neuromuscular 12 months. It can be associated with a known underlying transmission (Box 5-2). Muscle diseases can be further neurological disorder, or can be idiopathic, and is categorized into developmental myopathies, muscular associated with a poor neurodevelopmental outcome.
dystrophies, and metabolic myopathies. Disorders of Lennox–Gastaut syndrome consists of different types of neuromuscular transmission can be further categorized seizures which occur frequently and are difficult to con- into diseases of the neuromuscular junction and anterior trol. It usually manifests itself in the 3- to 5-year age group, horn cell diseases. This list is extensive and only the and is associated with severe mental retardation. Both most common and most important in pediatric anesthe- infantile spasms and Lennox–Gastaut syndrome are noto- riously difficult to control with anticonvulsant agents.
Muscle diseases, or myopathies, are characterized by There are a variety of treatment regimens that are muscle weakness and atrophy. Many children are sympto- individualized for each child and the particular type of matic at birth, while others are normal in early infancy seizure disorder (Table 5-2). Anesthesiologists should be only to develop weakness in the first few years of life.
familiar with the clinical indications and major side- The myopathies are of interest to anesthesiologists for two effects of the most commonly used anticonvulsants.
major reasons. First, some are associated with an increased Anesthetic concerns for children with seizure disor- risk of malignant hyperthermia (see Chapter 21); and ders will depend on coexisting morbidities and will be second, all are associated with development of life-threat- individualized depending on the mental status of the ening hyperkalemia after administration of succinyl- child. If necessary, children who require strict pharma- choline (see Chapter 19). Children with myopathies cologic control of their seizure disorder should have often require multiple surgical procedures throughout their oral anticonvulsants converted to the intravenous childhood. These include a muscle biopsy as a com- forms (or equivalent medications if intravenous forms ponent of the diagnostic work-up, insertion of a gas- are not available) during the preanesthetic fasting inter- trostomy or tracheostomy as weakness worsens, and val and during the postoperative period if oral intake is a variety of orthopedic procedures for alleviation of not possible. In most cases preanesthetic anticonvulsant As with neurological diseases, anesthetic considera- Most anesthetic and analgesic agents can be safely tions for children with muscle diseases will largely administered to children with seizure disorders. A possi- depend on the medical condition of the child, as there is ble exception is multiple doses of meperidine because its a wide spectrum of affliction, even between children metabolite, normeperidine, possesses proconvulsant with the same diagnosis. Even though central core properties. Nitrous oxide, sevoflurane, methohexital, eto- myopathy is one of the only diseases genetically linked to midate, and all opioids have been anecdotally associated malignant hyperthermia, most pediatric anesthesiolo- with seizure-like movements in both healthy and epileptic gists will perform a nontriggering anesthetic technique patients, without serious sequelae. In most of these cases for all children with myopathies. Use of nondepolarizing these movements were likely a benign form of myoclonus.
muscle relaxants will depend on the baseline strength Virtually all general anesthetic agents are anticonvulsants of the child. Careful titration of the neuromuscular in doses associated with loss of consciousness.
blocker based on train-of-monitoring is recommended.
Higher doses and shorter dosing intervals of neuro- Children with muscle weakness are at increased risk for muscular blockers are required in patients taking requiring postoperative mechanical ventilation, and thus, 4206 Litman-05.qxd 10/20/03 1:02 PM Page 4 PEDIATRIC ANESTHESIA: THE REQUISITES IN ANESTHESIOLOGY this possibility should be proactively addressed with the death before age 30 from either respiratory failure or Although no definitive genetic link to malignant hyperthermia has been found, most pediatric anesthesi- Developmental Myopathies
ologists consider these children to be MH-susceptible The developmental myopathies consist of a heteroge- based on anecdotal reports, and will perform a nontrig- neous group of congenital myopathies that are mostly gering technique. However, as stated above for CCM, nonprogressive, although some patients show slow clin- definitive proof of association between myopathies and ical deterioration. Most of these conditions are heredi- MH susceptibility is lacking. Use of inhalational agents, tary; others are sporadic. These include nemaline rod albeit for a relatively short period of time, appears to be myopathy, central core myopathy (CCM), and myotubular safe when intravenous access is not available.
myopathy. CCM is an autosomal dominant disease char- A less severe (yet debilitating) related disease is the acterized by hypotonia and proximal weakness at birth.
Becker-type muscular dystrophy. Similar features to Unlike other muscle diseases, there appears to be a pre- DMD include calf pseudohypertrophy, cardiomyopathy, disposition of CCM patients to malignant hyperthermia and elevated serum levels of CPK. However, the onset of susceptibility in the form of a genetic linkage to the weakness in Becker-type dystrophy is later in life than ryanodine receptor on chromosome 19. However, the lit- with DMD, and death often occurs at a later age than erature is conflicting, and the subject of myopathies and with DMD. The anesthetic considerations are identical susceptibility to malignant hyperthermia continues to Myotonic dystrophy is an autosomal dominant muscu- lar dystrophy that is characterized by the persistent con-tracture of both striated and smooth muscle after its Muscular Dystrophies
stimulation. Myotonia refers to the slow relaxation of a Although the muscular dystrophies are a group of contracted muscle and is observed in children over the unrelated disorders, there are four obligatory criteria that age of 5 years. All muscle tissues in every organ system distinguish them from other neuromuscular diseases: are affected, leading to widespread disease that begins mildly in the neonatal period but progresses through- out childhood. Additional clinical manifestations include cardiac, respiratory, and gastrointestinal dysfunction, (4) Degeneration and death of muscle fibers occur at endocrinopathies, immunologic deficiencies, cataracts, dysmorphic facies, intellectual impairment, and other neu- Duchenne-type muscular dystrophy (DMD) is an rologic abnormalities. Succinylcholine and cholinesterase X-linked recessive disease that, although present at inhibitors will exacerbate the myotonia.
birth, usually presents in early childhood as weak-ness and motor delay. Additional clinical manifesta-tions include pseudohypertrophy of the calves and Spinal Muscle Atrophy
markedly elevated baseline creatine phosphokinase Spinal muscle atrophy (SMA) is an inherited autosomal (CPK). Since weakness is greatest in the proximal muscle recessive disorder characterized by anterior horn cell groups, the child must rise from the sitting position in degeneration and is found as three clinical syndromes.
two steps: first leaning on the hypertrophied calves and Type 1 is called Werdnig–Hoffman disease and is the most then pushing the trunk up with the arms.This is referred severe beginning in early infancy. It is characterized by sig- to as Gower’s sign, and is nearly pathognomonic for one nificant muscle weakness and atrophy, except for diaphrag- of the muscular dystrophies. Eventually, progressive and matic sparing which occurs later in life. Type 2 presents severe muscle atrophy and weakness cause loss of the at between 6 and 12 months of age and has a more ability to ambulate. The most serious aspects of DMD prolonged, slightly milder course.Type 3 is the least debili- include a progressive cardiomyopathy and respiratory tating and is called Kugelberg–Welander disease. Cognitive failure secondary to ventilatory pump failure. Cognitive abilities remain unaffected in all forms of the illness.
abnormalities are usually mild. Most children become Life-expectancies vary with the severity of the disease; wheelchair-bound early in the second decade, with death occurs from repeated aspiration or lung infections.
4206 Litman-05.qxd 10/20/03 1:02 PM Page 5 An 11-month-old female is scheduled for a diagnostic muscle biopsy and open gastrostomy tube insertion. She has a history of hypotonia, developmental delay, and failure to thrive secondary to poor feeding effort. Chromosomal analysisis normal, and her physicians suspect she may have a mitochondrial myopathy. What is a mitochondrial myopathy? Is it associated with unique considerations for administration of general
anesthesia?
A mitochondrial myopathy is a type of genetic disease that is encompassed within a broad category of entities whose ori- gin is a defect in mitochondrial function, and thus interfere with normal adenosine triphosphate (ATP) production.Althoughmitochondrial defects can affect almost every organ system, those organs with high metabolic rates – such as the heart, brain,and skeletal muscle – are particularly vulnerable. ATP depletion results in accumulation of lactate, a byproduct of anaerobicmetabolism. Clinical manifestations include abnormalities of the heart (e.g., cardiomyopathy, conduction defects), skeletal mus-cle (e.g., atrophy, weakness), and central nervous system (e.g., seizures, encephalopathy, peripheral neuropathies, ophthalmo-logic manifestations), among many others. Examples of mitochondrial diseases include chronic progressive externalophthalmoplegia, Kearns–Sayre syndrome, Leigh’s disease, Leber’s hereditary optic neuropathy (LHON), mitochondrial myopa-thy, and myoclonic epilepsy with lactic acidosis and stroke-like episodes (MELAS syndrome). Treatment options are limited,and primarily supportive. Carnitine may lessen muscle weakness and fatigue in some children, and does not interact with anes-thetic agents.
Preanesthetic assessment of a child with a suspected or confirmed mitochondrial disease includes evaluation of comor- bidities – in particular, cardiac, respiratory, hepatic, and renal function. Premedication should be tailored to the individualpatient; respiratory depressants should be avoided in children with weak ventilatory drive.The overall goal of anesthetic man-agement is avoidance of metabolic stressors, such as hypoxemia and hypoglycemia, which may potentially exacerbate lacticacidosis. Clear glucose-containing liquids should be administered 2 hours prior to the anticipated induction of anesthesia.Allanesthetic agents have been used safely in patients with mitochondrial diseases, although prolonged use of propofol shouldbe avoided because of its association with lactic acidosis in the critical care setting. Neuromuscular blockers should be care-fully titrated to maintain one or two twitches on train-of-four monitoring, as patients with myopathies may demonstrate aunique sensitivity to these drugs. Steroidal neuromuscular blockers, which depend on adequate liver function for metabolismand termination of action, should probably be avoided.
Should this patient be considered malignant hyperthermia (MH)-susceptible?
There is no definitive genetic link between mitochondrial disease and MH susceptibility. In the presence of muscle atro- phy, elective use of succinylcholine is contraindicated, as it may cause life-threatening hyperkalemia. Inhalational agents havebeen used safely in patients with mitochondrial diseases.
How would you induce and maintain general anesthesia? Is a muscle relaxant necessary?
Induction and maintenance of general anesthesia will be routine: inhaled sevoflurane and N O for induction of anesthesia, or an intravenous induction agent if the child has intravenous access. Since this child has preexisting hypotonia, I don’t expectthat he will be able to adequately ventilate and oxygenate using a spontaneous ventilation technique.Therefore, I will likelyuse controlled ventilation, using either a laryngeal mask airway (LMA) or an endotracheal tube. Depending on the severity ofthe child’s hypotonia, I may choose to omit neuromuscular blockade from the induction regimen, since there are no surgicalrequirements for paralysis.
What are appropriate extubation criteria for this patient?
Extubation criteria for patients with hypotonia or developmental delay are ill-defined. The three criteria that are used in healthy children are: (1) sufficient muscle strength to maintain upper airway patency; (2) a regular respiratory pattern; and (3)wakefulness (e.g., spontaneous eye opening, following commands).The child in this case may demonstrate abnormalities forone or more of these criteria.Tracheal extubation will therefore become incumbent on the child attaining their preoperativeor baseline parameters.
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Box 5-2 Classification of Neuromuscular
Brenn BR, Brislin RP, Rose JB: Epidural analgesia in children Diseases of Childhood
with cerebral palsy. Can J Anaesth 45:1156–1161, 1998.
Choudhry DK, BR Brenn: Bispectral index monitoring: a com- Muscle Diseases
parison between normal children and children with quadriple-gic cerebral palsy. Anesth Analg 95:1582–1585, 2002.
Keyes MA, Van de Wiele BV, Stead SW: Mitochondrial myopathies: an unusual cause of hypotonia in infants and chil- dren. Paediatr Anaesth 6:329–335, 1996.
Theroux MC, Brandom B, Zagnoev M et al: Dose response of succinylcholine at the adductor pollicis in anesthetized chil- dren with cerebral palsy during propofol and nitrous oxide anesthesia. Anesth Analg 79:761–765, 1994.
Theroux MC,Akins RE, Barone C et al: Neuromuscular junctions in cerebral palsy: presence of extrajunctional acetylcholine receptors. Anesthesiology 96:330–335, 2002.
Wallace JJ, Perndt H, Skinner M:Anaesthesia and mitochondrial disease. Paediatr Anaesth 8:249–254, 1998.
GlycogenosesMitochondrial myopathiesLipid myopathies Diseases of Neuromuscular Transmission
Box 5-1 International Classification of
Epileptic Seizures
Organophosphate poisoningBotulismTick paralysis Partial Seizures
SensoryAutonomicPsychicComplex partial (impaired consciousness) Generalized Seizures
AbsenceTonicClonicTonic–clonicMyoclonicAtonic Unclassified Seizures
Infantile spasms (West syndrome)Lennox–Gastaut syndrome Reproduced with permission from Marino BS, Snead KL, McMillan JA eds:Blueprints in Pediatrics, 3rd edn, Blackwell Science Inc., Malden, MA, 2003.
4206 Litman-05.qxd 10/20/03 1:02 PM Page 7 Table 5-1
Types of Cerebral Palsy
Anatomical Location of Pathology
Symptoms
Quadriplegia, diplegia, and hemiplegia.The number of extremities affected and the degree of spasticity correlate with level of intelligence.
Dystonia (twisting position of torso), athetosis (purposeless movements of extremities), and chorea (quick, jerky proximal movements of extremities); seizures.
Table 5-2
Indications for and Side-effects of Anticonvulsants
Medication
Indications
Side-effects/Toxicity
Conventional DrugsCarbamazepine (Tegretol) Diplopia, nausea and vomiting, ataxia, leukopenia, Rash, anorexia, leukopenia, aplastic anemia Hyperactivity, sedation, nystagmus, ataxia Rash, nystagmus, ataxia, drug-induced lupus, gingival hyperplasia, Hepatotoxicity, nausea and vomiting, abdominal pain, weight loss, weight gain, anemia, leukopenia, thrombocytopenia Recently Developed DrugsGabapentin (Neurontin) Dizziness, ataxia, blurred or double vision, nausea, vomiting, and rash. A few cases of Stevens–Johnson syndrome reported.
Dizziness, somnolence, and tremor. May make absence epilepsy Tonic–clonic, partial, Lennox–Gastaut Somnolence, fatigue, weight loss, nervousness Reproduced with permission from Marino BS, Snead KL, McMillan JA eds: Blueprints in Pediatrics, 3rd edn, Blackwell Science Inc., Malden, MA, 2003.

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