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On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.55 no.6 Campinas Nov./Dec. 2005
Anesthesia and cerebral palsy*
Anestesia y parálisis cerebral
Március Vinícius M Maranhão, TSA, M.D.
Professor de Farmacologia do Instituto de Ciências Biológicas da Universidade de Pernambuco; Chefe do Serviço de Anestesiologia do Hospital Universitário Oswaldo Cruz; Co-Responsável pelo CET/SBA do Hospital da Restauração e Getúlio Vargas
OBJECTIVES: Cerebral palsy (CP) is a non-progressive disease induced by
CNS injury, which leads to patients' motor impairment. CP patients are often
submitted to surgical procedures due to usual diseases and some surgical situations
related with CP. The aim of this article was to review cerebral palsy aspects
of interest to anesthesiologists to allow an adequate pre, intra and postoperative
management of these patients.
CONTENTS: This article addresses cerebral palsy aspects such as etiology, classification, risk factors, pathophysiology, clinical presentation, diagnosis and therapies and, in addition to preoperative evaluation, preanesthetic medication, intra and postoperative management, postoperative analgesia and chronic pain.
CONCLUSIONS: Anesthesiologists play an important role in decreasing anesthetic-surgical morbidity and mortality of cerebral palsy patients. The understanding of different aspects of cerebral palsy pathophysiologies, in addition to those of associated diseases and their therapies is paramount, because it allows anesthesiologists to anticipate and prevent intra and postoperative complications in this type of patient.
Key words: ANESTHESIA, General; DISEASES, Neurological: cerebral palsy
Y OBJETIVOS: La parálisis cerebral (PC) es una enfermedad no progresiva
consecuente de una lesión en el sistema nervioso central, llevando a un
comprometimiento motor del paciente. El portador de PC, frecuentemente es sometido
a procedimientos quirúrgicos debido a enfermedades usuales y situaciones
particulares consecuentes de la parálisis cerebral. El objetivo de este
artículo, fue revisar aspectos de la parálisis cerebral de interés
para el anestesista, permitiendo un adecuado manoseo pre, intra y posoperatorio
en este tipo de paciente.
CONTENIDO: El artículo aborda aspectos de la parálisis cerebral como etiología, clasificación, factores de riesgo, fisiopatología, cuadro clínico, diagnóstico, terapéuticas utilizadas bien como evaluación pre-operatoria, medicación pre-anestésica, manoseo intra y posoperatorio, analgesia posoperatoria y dolor crónico.
CONCLUSIONES: El anestesista desempeña un papel importante en la disminución de la morbidez y mortalidad anestésico-quirúrgica en pacientes portadores de parálisis cerebral. El conocimiento de la fisiopatología de los diferentes tipos de parálisis cerebral bien como de las enfermedades asociadas y sus terapéuticas es imprescindible, pues permite al anestesista anticipar y precaver complicaciones intra y posoperatorias en este tipo de paciente.
Cerebral palsy (CP) is a non-progressive disease affecting movements and posture, with different etiologies resulting in central nervous system injury. These occur during early brain development stages, in the pre, peri and post-natal period, leading to children's motor functions involvement 1-5.
The incidence is approximately 2:1000 live births in developed countries, and this rate has not changed in recent years. There are evidences that the incidence increases in premature children with low weight at birth 6.
Clinical presentation varies widely, from mild monoplegia with normal intellectual capacity, to severe motor spasticity throughout the body associated to mental retardation 1,2.
In general, CP children have at least one additional disability triggered by CNS injury, such as cognitive impairment, sensory losses (seeing and hearing), seizures, behavioral changes and chronic systemic diseases (orthopedic, gastrointestinal and respiratory) secondary to the primary presentation 7.
Medical care progresses have redirected the management of cerebral palsy children from a passive and supporting phase to a more active phase involving surgical treatment. As result, there has been increased participation of anesthesiologists in CP patient's perioperative care 2,4.
The understanding of the etiology, of clinical involvement and therapies, including the familiarity with drugs used in these patients, may help anesthesiologists in the management of CP children in pre, intra and postoperative periods 1.
This is a multifactorial disease. In a low percentage (6%) of cases, it is caused by hypoxia during labor and frequently result is a spastic quadriplegia. Although there are many cases of unknown etiology, there are evidences that prenatal causes may result in fetal neurological complications manifested after birth, which have been erroneously diagnosed as perinatal asphyxia 1,2,8.
Cerebral palsy in premature neonates is often a consequence of periventricular leukomalacia due to periventricular hemorrhage. Another possible cause is intrauterine ischemic injury, which may lead to premature labor and white matter injuries 1.
The etiology in term neonates is not clear, but may involve immature brain injury in early pregnancy, stroke, prenatal infection (toxoplasmosis, rubella, cytomegalovirus, herpes), thyroid diseases and genetic changes 1,2.
A recent study from the period 1970-1999 with 70824 neonates has found an incidence of CP patients with pre and perinatal etiology of 2.3:1000 neonates. Most patients had low weight at birth (< 2500 g). Frequently the low weight neonates had intra or periventricular hemorrhage, periventricular leukomalacia or brain infarction as most frequent perinatal / neonatal etiologies. In the case of normal weight patients the major perinatal CP cause was hypoxic-ischemic encephalopathy 9.
The major postnatal causes of this syndrome were meningitis, viral encephalitis, hydrocephalus, trauma, brain veins and arteries occlusion, surgical injuries and their treatment 1,3.
A study involving the period 1976-1990 has shown that major postnatal cerebral palsy causes are infections (50%), vascular abnormalities (20%) and trauma (18%) 10.
Although controversial, it seems to be a correlation between the use of magnesium and lower risk of cerebral palsy in neonate patients weighing below 1500g who were exposed to the drug in the prenatal period to prevent eclampsia or to inhibit premature labor.
Different mechanisms have been proposed for this effect, such as anti-oxidant effect protecting the brain against noxious mediators, vascular tone stability preventing or decreasing brain blood flow changes, decreased post-hypoxia reperfusion injury possibly by blocking NMDA receptors with decreased intraneuronal calcium levels. Magnesium may decrease intrauterine infection effects by decreasing toxin release and activating cytokines and protecting fetal brain.
Arguments against magnesium beneficial effects are based on the fact that pre-eclampsia itself may protect brain against cerebral palsy. Neonates of pre-eclamptic mothers tend to have lower gestational age and low weight at birth. However, they are more mature and less vulnerable to brain injury as compared to low weight neonates of non pre-eclamptic mothers. Prenatal glycosteroids are associated to significant decrease in severe periventricular and intraventricular hemorrhages and may have a neuroprotecting effect decreasing the incidence of cerebral palsy 1,2,11-13.
Cerebral palsy is classified in spastic, diskinetic (including choreoathetoid and dystonic), ataxic, hypotonic and mixed, according to the type of neuromuscular involvement.
Based on topographic distribution, spastic cerebral palsy may be classified in quadriplegic (affecting the four limbs and more severe in upper limbs), diplegic (affecting lower limbs with minimum involvement of upper limbs) and hemiplegic (spasticity affects upper and lower limb of one side, frequently with more severe involvement of the upper limb) 1-3,14,15.
Spastic CP is the most frequent, affecting 70% of cerebral palsy children. It presents prolonged contractures in elbow, wrist, hip, knee and ankle. Diplegia and hemiplegia have a better functional prognosis. Diplegia is often associated to prematurity. Mental retardation and epilepsy are common in quadriplegic CP.
In quadriplegic spastic cerebral palsy, nerves controlling mouth, tongue and pharynx movements may be impaired, which may lead to feeding and hydration difficulties and may require nasogastric catheter or gastrostomy. Aspiration pneumonia is frequent. There is low probability of functional improvement for these patients 1,2.
Diskynetic CP is seen in approximately 20% of CP children. It may be associated to deafness, dysarthria and sialorrhea. Seizures are present in 25% of patients. There has been major decrease in kernicterus with decreased incidence of this type of CP with exchange transfusion for incompatible blood groups 1,2.
Balance is impaired in ataxic CP and speech changes are common. Mental retardation and epilepsy are frequently seen. Functional improvement in this group is very unlikely 1,2.
Mixed forms are seen when two or more CP types are present. Spastic and diskinetic CP is the most common association.
Risk factors before pregnancy are associated to women with long menstrual cycle intervals, short (less than three months) and long (more than three years) intervals between gestations, history of spontaneous abortion and family history of motor disease 3.
Risk factors during pregnancy is related to low social status, congenital malformations, delayed intra-uterine growth, twin pregnancy, fetal presentation abnormalities, maternal hyperthyroidism, use of thyroid hormone and estrogens 3.
Perinatal risk factors are represented by placenta previa and intra-partum anoxia, in addition to nonspecific changes such as fetal bradycardia, presence of meconium, low Apgar scores and neonate encephalopathy 3.
Very seldom cerebral palsy is diagnosed in the first year of life, even with the presence of suggestive CP signs, such as unsatisfactory development, spasticity or lack of coordination. Early medical follow up aims at determining whether abnormalities are caused by cerebral palsy or by progressive motor impairment.
It is important to emphasize that the relationship between central nervous system injury and functional impairment may change along time. Muscle tone or movement abnormalities present in the first weeks, may gradually improve during the first year of life and, in some cases, clinical presentation may disappear 3. On the other hand, nonspecific motor signs, such as hypotonia, seen in the first weeks and months of life, may evolve after the first or second year of life to spasticity and extrapyramidal symptoms 3. It is believed that axonal myelinization and neuronal maturity of basal ganglia are needed before the development of spasticity, dystonia and athetosis.
Specific CP type is seldom determined before children reach 18 months of age. Tests, such as electroneuromyo- graphy, muscle biopsy, CT scan and MRI may be performed to differentiate CP from other diseases 3.
REASONS FOR TREATING CEREBRAL PALSY CHILDREN
Cerebral palsy is incurable with lifetime problems. However, a lot may be done for patients to reach the maximum possible independence. Physical therapy, occupational therapy, jackets and orthopedic surgeries may improve muscle control and ambulation 2.
The aims objective of spasticity treatment is a functional improvement to preserve or enhance movements and decrease contractures, spasm and pain severity. Major objective is improving independence and helping the daily care of more severely affected patients 2.
Nutritional support helps preventing malnutrition, infection and renal complications 2.
Speech therapy may improve speech and improve feeding problems 2.
Many CP children, if free from mental retardation and severe physical disabilities, grow normally and go to regular schools. Others need continuous physical therapy, special education and have severe limitations to perform daily tasks, requiring some type of treatment and assistance for the rest of their lives. However, even severely affected children may benefit from education and training 3.
Parents should be informed and counseled, to help them understand their children problems and potential, and face difficulties as they may appear. To help children reach their maximum potential, careful attention of parents may be combined with the help of public and private institutions, such as institutions of community health and rehabilitation for humanitarian purposes 2.
Prognosis in general depends on cerebral palsy type and severity. More than 90% of CP children survive until adulthood. Only those with more severe neurological impairment (unable to perform any personal care) have lower life expectancy 3.
ANESTHETIC CONSIDERATIONS FOR CP CHILDREN
These children need special attention due to multiple systems involvement 1. One should not forget that they have feelings and emotions and should be attentively and carefully treated 1.
CP children are submitted to surgical procedures for numerous reasons, that is, from usual surgical conditions until unique CP-induced situations 2.
In case of patients with speech problems may be used cards or computers for communication and these resources should be available whenever possible 1.
Diskinetic CP patients are in general smart, however with major communication difficulties. It is important to give these children enough time to communicate within their limitations 1.
Questionnaires to be filled in by parents or tutors, detailing how their children communicate and react to pain, hunger and other situations are important and may help the medical team in understanding their behavioral manifestations. Parents and escorts are the most adequate people to mitigate children's fears and anxiety, in addition to being their strongest protectors.
So, all consideration and respect should be given to parents and escorts and their opinions. Parents may be aggressive and highly protective with their children. These manifestations should be understood as a consequence of previous experiences, stress, frustration, anger and probably guilt 16.
Surgical procedures are being increasingly performed in cerebral palsy patients. Every procedure has to be evaluated in terms of morbidity and mortality as well as of the probability of improving quality of life. This has to be clearly and objectively discussed with relatives, being important the informed consent signed by those in charge of the children 2.
Adequate preoperative evaluation is critical to assure a relaxed perioperative period. These children should be preferably evaluated by a multidisciplinary team, which should include the anesthesiologist. Cognitive, communication and behavior problems, coexisting diseases and drug therapy may influence the anesthetic management of these patients 1.
CP children may present multiple systems involvement and a thorough investigation of those more frequently involved is paramount during preoperative evaluation.
Gastroesophageal reflux is common and may cause respiratory complications, especially in those patients with severe neurological deficit. Esophageal motility changes, decreased cardia tone and spinal deformities may contribute for this situation 1,17.
It may be difficult to diagnose reflux. Suggestive signs include dystonic movements related to posture (Sandifer syndrome). Insomnia may indicate esophageal reflux or spasm 1.
Fundoplication, gastrostomy and esophageal dilatation due to esophagitis-induced stenosis are the second most frequent cause for surgical procedures in these patients, only second to orthopedic procedures 1.
Severe sialorrhea may be debilitating for CP children. It may be related to pseudobulbar paralysis with swallowing impairment worsened by poor temperature control. Anticholinergic drugs may be indicated. In some cases, surgery to reimplant salivary ducts is indicated 1,18,19.
A small group of CP children is unable to be orally fed due to difficulties in chewing and swallowing, which leads to malnutrition and very often requires nasogastric catheter or gastrostomy 20.
Preoperative nutritional support may decrease the incidence of malnutrition-induced postoperative complications. It is important to emphasize that malnutrition may depress immune response. Malnutrition-induced hydroelectrolytic unbalance and the use of laxatives may require treatment. Anemia is frequent 20.
Respiratory complications are the most frequent cause of CP children death, among them pulmonary aspiration due to gastroesophageal reflux, repetition respiratory infection and chronic lung disease, which may be worsened by the difficulty in coughing with precarious excretion of secretions 17,21.
Very often, respiratory system changes may go unnoticed due to difficult communications and to neurological impairment preventing the evaluation of tolerance to exercise 1.
Scoliosis may lead to restrictive pneumopathy with cardiopulmonary involvement 1.
Although pulmonary function tests are indicated, it is virtually impossible to perform them in CP patients, especially those with severe neurological impairment 1,2,22.
Other relevant aspects are the possibility of bronchopleural dysplasia with tracheomalacia, airway irritability and obstructive pulmonary disease associated to prematurity 21,23.
Preoperative physical therapy, bronchodilators and antibiotics optimize intra and postoperative care 1.
Airways should be thoroughly evaluated for the possibility of difficult intubation due to caries, loss of teeth and increased incidence of TMJ dysfunction 24. CP children have a higher incidence of malocclusion 25. Its severity is higher in children with further neurological impairment. Malocclusion generally does not lead to difficult intubation or airway maintenance with facial mask 1.
When airway evaluation is not possible, the review of previous anesthetic records may be important.
Cerebral palsy children have variable degrees of spasticity in different skeletal muscle groups, causing contractures and deformities in different upper and lower limb joints. Among them there are changes in bending and internal rotation of hip joint due to impairment of adductor and flexor muscles, in addition to plantar ankle bending changes by the involvement of tendons. These children often need surgical procedures, such as tendon elongation, hip adductor and ileopsoas release and femoral osteotomy 26.
Decubitus ulcers and skin infections may be also seen 2.
It is present in approximately 30% of CP patients. It is more frequent in spastic hemiplegia and less frequent in the ataxic and coreoathetoic forms. Generalized and complex partial tonic-clonic seizures are frequent. Anticonvulsants should be maintained until the surgery date and restarted as soon as possible in the postoperative period 1,7,15.
VISUAL AND AUDITORY CHANGES
Approximately 40% of CP children have visual abnormalities, including nearsightedness, visual field defects and cortical blindness. Premature children have further visual impairment secondary to prematurity retinopathy. Strabismus is common and may lead to amblyopia. Prematurity retinopathy and amblyopia may require surgical treatment 1,14.
BEHAVIOR AND COMMUNICATIONS CHANGES
Mental retardation is present in approximately one third of CP patients and others may present learning deficits 7. Normal intelligence is seen in more than 60% of hemiplegic children, however in less than 30% of those with spastic or mixed quadriplegia. Mental retardation may be severe in 50% of patients 27. Attention deficits are especially common in children without mental retardation, while some patients with intellectual deficits may occasionally suffer behavioral changes. Aggressiveness and hyperactivity may also be present. Depression and emotional lability are common in adolescents 14,28.
Difficult and irregular sleep may be present and require sedatives 14.
COMMON SURGICAL PROCEDURES IN CEREBRAL PALSY CHILDREN
Orthopedic procedures, such as loose tissue release, are commonly performed in these children to improve contractures. The specialist shall define through periodic tests and therapists' information, which deformities are worsening, or delaying treatment evolution. The surgeon, however, has to be convinced that a certain surgery will really benefit the patient and that this is the right moment to operate.
All favorable and unfavorable factors should be evaluated. The family must agree and be thoroughly explained and oriented about difficulties and must be willing to cooperate 29. Currently, there is a trend in orthopedic surgery to perform multiple procedures to prevent repetition procedures, involving tenotomies and / or osteotomies in different levels of both extremities. They are in general performed between 6 and 12 years of age 1,2,29.
Scoliosis correction is associated to acute and sometimes prolonged respiratory function deficit, even when thoracotomy is not performed. Currently, surgeons are adopting thoracoscopy to decrease respiratory system morbidity 2.
It is important to emphasize that major blood losses (more than 50% of circulating blood volume) are 6.9 times more frequent in neuromuscular disease patients, including cerebral palsy, as compared to neuromuscular disease-free patients 30.
Gastroesophageal reflux is common in CP children, often requiring corrective procedure. Conventional surgery is associated to significant morbidity and laparoscopy is currently the technique of choice. It is important that anesthesiologists are aware of physiological changes associated to children's pneumoperitoneum in this type of procedure, such as increased CO2 expired fraction, PaCO2, cardiac index, heart rate, blood pressure and maximum inspiratory pressure 31. The need for intensive therapy seems to be minimized with laparoscopy. Although postoperative pain seems to be lower, epidural analgesia may be required to prevent pain-induced muscle spasm 2,15,32.
Inguinal Hernia Correction
This is the most frequent CP neonates surgery in the first days of life, especially in those weighing less than 2000 g. It is probably due to increase in intra-abdominal pressure associated to abdominal wall tone increase. Correction before hospital discharge improves patients' comfort and nutrition without increasing morbidity 2.
Other common surgical procedures include teeth extractions and restorations, gastrostomy and tracheostomy 1,2. Neurosurgical procedures are performed in some centers, including ventro-lateral thalamotomy to control shivering, selective cortical ablation for seizures and posterior selective rhizotomy to decrease muscle tone 1,33.
DRUGS COMMONLY USED FOR CEREBRAL PALSY PATIENTS
It is extremely important that anesthesiologists know the drugs used by CP patients, as well as their pharmacokinetic and pharmacodynamic profiles. Commonly used drugs by CP children are anticonvulsant, anti-spastic, anticholinergic, anti-reflux, antacids, laxative and antidepressant drugs. Anti-spastic, anticonvulsant and antidepressant drugs should be maintained in the preoperative period.
CP brain injury impairs descending inhibitory neurons leading to inadequate release of gamma aminobutyric acid (GABA) and relative increase in excitatory neurotransmitters, especially glutamate and aspartate, increasing muscle tone 1,2,34. Excessive alpha motoneurons stimulation results in spasticity with simultaneous contraction of agonist and antagonist muscle groups.
Baclofen acts as GABA(B) receptors agonist in spinal cord dorsal horn (Rexed, II and III laminae) 1,2. The activation of these spinal cord receptors inhibits pre-synaptic calcium inflow and blocks excitatory neurotransmitters release (glutamate and aspartate) resulting in hyperpolarization.
This pre-synaptic inhibition may be increased by post-synaptic drug binding, increasing potassium conductance 35. Baclofen is used to decrease muscle spasm-induced pain and may delay the development of contractures. GABA(B) receptor agonists decrease neurotransmitters release, such as substance P and the peptide related to calcitonin gene, both excitatory in pain transmission 35. For patients unable to walk, the drug may help normal daily activities and hygiene care.
Oral baclofen poorly crosses blood-brain barrier and its adverse effects are sleepiness, ataxia, dizziness, lethargy, euphoria, hallucinations, depression, headache, hums, paresthesias, speech changes, vomiting, diarrhea or constipation, shivering, insomnia, visual defects, skin erythema, pruritus, urinary abnormalities and liver function impairment 1,2,35. Baclofen should be cautiously administered to patients with peptic ulcer, severe psychiatric disease or seizures, which may be exacerbated by the drug 35. High doses may result in comma, apnea, cardiac conduction changes, hyporeflexia, hypotonia and seizures 36.
Low spinal baclofen doses decrease spasticity better than when orally administered, and has few adverse effects. Central nervous system concentration is 10 times higher as compared to oral administration 1,2. Decreased spasticity is observed 24 to 48 hours after beginning of infusion. Overdose may be sudden or insidious and may be manifested by sleepiness, respiratory and cardiovascular depression, rostral hypotonia progression or unconsciousness 1,2,34.
These adverse effects are uncommon. They are usually related to pump programming mistake. Major spinal baclofen complications are infection (5%), catheter disconnection and fracture 1,37. Other adverse effects include apathy, urinary retention and lower limbs weakness requiring drug dose decrease. Simultaneous use of benzodiazepines or opioids and spinal baclofen increases the risk of respiratory depression 34,38.
Intravenous physiostigmine and flumazenyl may revert baclofen overdose effects, however high overdoses may require infusion withdrawal, respiratory support and removal of 30 to 40 mL CSF through lumbar puncture. A further study has not confirmed the efficacy of flumazenyl to revert baclofen overdose effects 37,39,40.
Sudden oral or spinal baclofen withdrawal may cause seizures, hallucinations, disorientation, diskinesias and pruritus, which may persist for up to 72 hours 41. Doses should be gradually decreased for two weeks 35. Oral baclofen may cause bradycardia and hypotension during general anesthesia 42,43.
It is important to remember that in addition to their post-synaptic actions, some anesthetic drugs (benzodiazepines, barbiturates and propofol) exacerbate gabaergic inhibitory transmission through pre-synaptic mechanism and may exacerbate baclofen effects, although general anesthetics act preferably on GABAA and baclofen action is on GABAB receptors 34,36,44,45. Baclofen decreases glutamate release, decreasing excitatory transmission and may exacerbate the antagonist effect of ketamine-mediated NMDA receptors with increased analgesic action, although there are no clinical evidences in the literature 34. It has been shown that baclofen exacerbates morphine and fentanyl effects 34.
Botulin Toxin Type A
Botulin toxin A is indicated when spasticity interferes with function and the child is considered too young for surgical spasticity correction.
It acts on pre-synaptic nervous terminal preventing acetylcholine release in the mioneural junction producing functional muscle dennervation 1,2. These are reversible and dose-dependent effects. After being injected in the target muscle there is fast binding and affinity causing minor systemic drug absorption with minimum toxicity 1,2. Respiratory support and anti-toxin treatment are indicated in case of toxicity 1.
Botulin toxin effect is not immediate, onset varies from 12 hours to 7 days and duration of action from 2 to 6 months; occasionally, effects remain for a longer period. The production of antibodies against botulin toxin increases and requires that injections are administered at at least 3-month intervals 1,2,46.
Most frequent adverse effect is mild discomfort at injection site in 33% to 50% of patients, which may persist for 1 to 2 days. Other effects include fatigue and transient muscle weakness in the muscle where the drug was injected. Ge- neralized muscle weakness as a consequence of systemic effect is very uncommon. Prolonged use of the drug may result in muscle atrophy. Botulin toxin counterindications include coagulopathies and infections at injection site 1,47,48.
Botulin toxin is in general injected under general anesthesia and procedures take 10 to 15 minutes. In cooperative children, injection may be performed after eutectic mixture of local anesthetics (EMLA®) on the skin, avoiding the need for general anesthesia. Most important botulin toxin interaction with anesthetic drugs is exacerbation of neuromuscular blocker effect, however without clinical significance 1,49.
Botulin toxin administration 5 to 10 days before surgical procedure may decrease postoperative pain secondary to muscle spasm 50.
Diazepam and other benzodiazepines (clonazepam, lorazepam) increase GABA-mediated pre-synaptic inhibition decreasing spasticity. Normally they are orally administered. Adverse effects include lethargy and development of tolerance 2,51.
Clonidine decreases muscle tone with consequent improvement of spasticity in patients not responding to diazepam and baclofen 1.
Most common barbiturate used as anticonvulsant is phenobarbital. Cognitive and behavioral changes have limited its use, being currently considered second line drug to treat epilepsy 51. Anticonvulsant action is a consequence of its activity in modulating GABA and glutamate post-synaptic action.
Adverse effects are sedation in adults and children, irritability and hyperactivity in children, tolerance, depression and mental confusion in the elderly, effects on cognition, skin changes, megaloblastic anemia, nistagmus, ataxia, abnormal collagen deposition, coagulation changes and hemorrhages in neonates.
Phenobarbital stimulates liver microsomal enzyme system and there may be changes in response to liver metabolized drugs 26,51.
Vigabatrine is a transaminase GABA enzyme inhibitor, originally developed to treat epilepsy. It impairs GABA metabolism and may be used to treat spasticity 2.
Common adverse effects are sleepiness, weight gain, ataxia, diplopia and vertigo. There may be psychotic states, especially in patients with psychiatric history, including mental retardation 52.
It is a clonidine-derived drug probably inhibiting central aspartate release and decreasing muscle tone.
Adverse effects may be observed, such as dry mouth and muscle weakness. Uncommonly it may cause reversible liver function test abnormalities, which disappear after drug withdrawal. Mild hypotension has been reported. Hepatitis and hallucinations are uncommon. Spinal administration is under investigation. Tolerance to sedative, but not to antispastic effects, has been described 2,35,53.
It inhibits skeletal muscles sarcoplasmic reticulum calcium release decreasing muscle tone. It is used orally to treat spasticity. There is no effect on central spasticity mechanism.
Adverse effects, such as muscle weakness, diarrhea, asthenia, blurred vision, nausea and skin changes have been observed. Liver function test abnormalities have been described 2,51. Dantrolene induces hepatitis in approximately 0.5% of patients treated for more than 60 days. Fatal hepatitis is present in 0.1% to 0.2% of chronically treated patients. So, liver function should be monitored when the drug is used for more than 45 days 51. There may be pleural effusion with prolonged therapy 51.
This is a gastrointestinal prokinetic drug stimulating gastric emptying, increasing lower esophageal sphincter tone and small and large intestine motility by increasing acetylcholine release in nervous terminals of gastrointestinal mucosa myoentheric plexus 51. It is used to treat gastroesophageal reflux.
It may promote increased QT interval and severe ventricular arrhythmias. This complication is more frequent in patients with liver dysfunction and simultaneous use of drugs impairing its metabolism 2.
Valproic acid is used to treat epilepsy.
It may increase bleeding due to platelet dysfunction, thrombocytopenia or acquired Von Willebrand type 1 factor deficiency. These changes are dose-dependent. Decreased dose, and seldom its withdrawal, normalizes coagulation. Preoperative coagulation tests are important for patients under sodium valoproate 2. Most important adverse effect is liver toxicity, present in approximately 0.2% of children below two years of age 51. There may be increased pharmacological effect of phentoine and diazepam if simultaneously used 51.
Adverse effects are sedation, dizziness, diplopia, nausea, vomiting, diarrhea, skin erythema, aplastic anemia, thrombocytopenia, jaundice, oliguria, hypertension and arrhythmias. Chronic leucopenia may be observed. High doses may cause inadequate antidiuretic hormone secretion syndrome leading to hyponatremia 51.
It promotes enzyme induction of itself and of other drugs, such as contraceptives, valproic acid, steroids, anticoagulants and anti-psychotics 51. Drugs inhibiting carbamazepine metabolism, such as cimetidine, propoxifen, diltiazen, verapamil, isoniazide and erythromycin exacerbate drug effect and may cause toxicity 51.
Anticonvulsant drug regulating neuronal excitability thus propagating convulsing activity by regulating sodium transportation and probably by calcium transportation through the neuronal membrane. This membrane stabilizing effect is selective for cerebral cortex although the effect may be extended to peripheral nerves 51.
Phentoine adverse effects include nistagmus, ataxia, diplopia, dizziness, peripheral neuropathy, gums hyperplasia, acne, hirsutism, allergic reaction, hyperglycemia, megaloblastic anemia, liver toxicity and gastric irritation. It promotes enzyme induction of some liposoluble drugs, such as carbamazepine, valproic acid, anticoagulants and steroids 51.
CP patients are often submitted to multiple hospital admissions, which may lead to severe anxiety.
Benzodiazepines should be considered due to their anxiolytic and myorelaxant properties; however there may be unexpected responses and risk-benefit ratio should be taken into consideration. Antacids, gastrokinetics and drugs decreasing secretions may be indicated 1. Eutectic mixture lidocaine-prilocaine (EMLA®) should be used at venous puncture site in poorly cooperative patients or those in who puncture pain may lead to major stress.
It is important to gain children's trust. Ideally, only the anesthesiologist in charge of inducing anesthesia should be part of the multidisciplinary team.
Most CP children are extremely anxious due to poor understanding and communication difficulties, especially those with severe deficit. They are often submitted to repeated surgical procedures, with considerable impact of these experiences 1,2. Fear may make parents' or escort's separation difficult. It is important to highlight that parents or escorts are able to communicate with the children, which is not true for medical professionals such as the anesthesiologist. So it is important to have those people close to patients during anesthetic induction and in the post-anesthetic recovery unit. In addition to optimizing patient's general clinical conditions, the anesthesiologist should discuss with the family the perioperative risk and the anesthetic technique to be used 2.
The detection of perioperative risk factors in CP children based on preoperative results is currently being emphasized.
Children unable to walk, with severe neurological deficit, with major mental retardation, with gastrostomy or tracheostomy, are at higher risk for intra and postoperative complications 2.
Severe scoliosis, malnutrition and hypovolemia, which may increase the incidence of infections and renal injury, as well as circulatory complications, such as deep vein thrombosis, are risk factors for postoperative complications 2.
Venous access may be difficult due to spasticity, dystonia or simply refusal. This difficulty is also frequent in children with repetitive admissions in special baby units or neonatal ICU and who have been submitted to multiple punctures 1,2,22. These children may be dehydrated due to abnormal response to thirst, in addition to prolonged preoperative fasting, becoming susceptible to pre-renal and renal failure. The impact of this complication may be minimized by carefully monitoring urinary output, especially in procedures with major blood losses 1,2.
Basic monitoring (noninvasive blood pressure, pulse oximetry, ECG and capnography) should be adopted for all patients. In critically ill patients or those submitted to major surgeries, invasive monitoring is recommended 1,2.
Airway maintenance during anesthetic induction may be difficult due to sialorrhea, making inhalational induction difficult and risky 1,2. Antisyalogogue medication, such as atropine, may be beneficial, however, due to secretions drying and difficult expectoration, there may be increased incidence of pulmonary infection 2. In this situation, tracheal intubation should be always performed, as well as in patients with history of gastroesophageal reflux 54. Children with gastroesophageal reflux are more vulnerable to aspiration during tracheal intubation and extubation 20.
Patients with severe spinal malformations may have difficult tracheal intubation and pediatric bronchofibroscopy material should always be available 21. Generalized cervical column ligaments loosening, atlanto-axial subluxation or foramen magnum stenosis may predispose to spinal cord compression, especially during tracheal intubation, with possibility of triggering quadriparesia 21.
Although CP children are in general small for their age, tracheal tube gage should be in accordance to age, as it is normally done. If rapid sequence induction is needed, lack of cooperation may impair the technique. The risk between fast and safe airway and slow inhalational anesthesia in a non-cooperative child should be evaluated. For long surgeries, frequent aspiration of oro or nasopharynx should be performed 1.
CP children may develop upper airway obstruction after tracheal extubation, secondary to laryngospasm and/or masseter spasm, which may be triggered by muscle spasticity, slow inhalational anesthesia recovery and postoperative pain. Upper airway obstruction may evolve to negative pressure pulmonary edema with the need for mechanical ventilation 55. Tracheal extubation should be achieved with the patient alert and normothermal 15.
Notwithstanding the possibility of major respiratory complications during general anesthesia, a broad prospective study with patients with different types of cerebral palsy submitted to CT scan and with the use of laryngeal mask and sevoflurane has not shown a higher incidence of perioperative respiratory complications in those patients as compared to the control group 56.
Antiemetics are recommended due to the high incidence of postoperative nausea and vomiting, especially when opioids are administered 33.
Careful positioning on the operating table is critical for spastic CP children to prevent nervous and/or muscle injuries. Contractures may further impair positioning 1,2,21,23.
There are different responses to anesthetic drugs. There may be resistance to nondepolarizing neuromuscular blockers in patients with and without anticonvulsants, although without clinical significance. This abnormal response may be due to the interaction with anticonvulsant agents (increased liver excretion, increased protein binding, and acetylcholine receptors upregulation) and chronic immobilization 1,2,57-60. There is probably no sensitivity to succinylcholine, although it has been described by some authors, however without clinical significance 1,2,61. In spite of skeletal muscle spasticity, succinylcholine does not promote abnormal potassium release in CP patients 15,20. TOF stimulation response may not evaluate neuromuscular block condition in patients with severe spasticity, and blockade intensity may be underestimated.
CP children have decreased inhalational agents MAC as compared to control groups. Halothane MAC is 20% lower in CP children and 30% lower if combined with anticonvulsants 1,2,62.
A study with bispectral index (BIS) in CP children induced and maintained with nitrous oxide and sevoflurane, has shown that BIS changes are similar to normal children, however absolute values observed in CP children are lower when awaken and in different sevoflurane concentrations as compared to the control group 63.
These results were confirmed by a national study showing that baseline EEG-BIS values in CP patients receiving general anesthesia with sevoflurane and nitrous oxide were lower as compared to the control group, with statistically significant differences. In the first five minutes after sevoflurane withdrawal, BIS values of CP patients took longer to increase, probably because anesthetics have remained for a longer period in the central nervous system, which may be justified by the degree of neuronal injury which generates blood flow deficiency in certain brain regions, delaying the return to consciousness 64.
Costa et al. 65, in a comparative study, have evaluated through BIS the use of nitrous oxide in children with or without CP. In studied concentrations, nitrous oxide has mildly decreased EEG-BIS in the observed groups, thus ratifying its minor hypnotic power. Somatosensory evoked potential analysis has shown decrease in amplitude and increase in latency of potentials in spinal cord and especially in the brain, being these decreases more intense in patients with cerebral palsy, which shows that those patients are more sensitive to nitrous oxide when administered as single agent.
Sevoflurane, more than isoflurane, presents epileptogenic activity in epilepsy patients. Hyperventilation and nitrous oxide supplementation have suppressed this effect being this association safe for epilepsy patients with cerebral palsy 66,67.
Hoffmann's reflex or H reflex is a reflex measuring motoneurons excitability. Cerebral palsy children often present high amplitude of this reflex. Its maximum amplitude is significantly decreased by nitrous oxide, that is, abnormal medullary reflexes seen in spastic diplegias may be attenuated by nitrous oxide, which should be considered during physiological spinal cord monitoring during anesthesia 68.
Several anesthetic agents are anticonvulsants, thus safe for patients with history of seizures. Enflurane, ketamine and etomidate should be avoided in epilepsy patients 1,69.
Although ketamine should be avoided in patients with history of seizures, the drug has been used alone or associated to halothane in patients with cerebral palsy submitted to outpatient procedures, and most common complications are tachycardia, repetitive vomiting and psychomotor agitation 15.
Propofol induces involuntary movements more a consequence of myoclonias than of epileptic origin. Few cases of neuroexcitatory symptoms have been reported with propofol, however most studies show that the drug is safe for cerebral palsy patients. Pain at injection may be a limiting factor for the use of propofol in cerebral palsy children 1,69,70.
Prolonged meperidine administration in kidney disease patients may result in the building up of normeperidine, which is an epileptogenic 1.
Latex allergy has been reported in CP patients, leading to severe bronchospasm and atelectasy 1,8,71. This is probably due to the large number of procedures to which they are often submitted with consequent exposure to latex. A history of sensitivity should be always investigated in all CP patients, such as sibillus, allergic rhinitis, skin manifestations, pruritus and edema when exposed to latex, as well as adverse reactions during previous anesthesias. In case of perioperative anaphylaxis, latex allergy should always be considered 1,2,71,72.
Intraoperative hypothermia is common in those children due to changes in temperature regulation secondary to hypothalamus dysfunction. The loss of muscle and fatty tissues in malnourished children may be the cause for hypothermia. Prolonged abdominal inflation with CO2 during laparoscopic procedures may increase heat loss. Normothermia may be difficult in spite of warmed blankets, active heating devices (forced air) and venous and irrigation fluids warming. Operating room temperature control is highly recommended. Gases humidification and warming may be beneficial, in addition to decreasing airway secretions retention 1,2,15. It is important to highlight that hypothermia may slow anesthetic recovery in CP children 15.
Most major procedures in CP children should, whenever possible, be performed with general anesthesia associated to regional anesthesia due to the excellent quality of intra and postoperative analgesia, with consequent decrease in postoperative pain and spasm 1,2,54,73.
Regional anesthetic techniques, such as epidural anesthesia (lumbar or caudal), spinal anesthesia and combined spinal-epidural anesthesia, with local anesthetics used alone or associated to opioids and alpha2-adrenergic agonists (clonidine) have been safely used in cerebral palsy patients, with more frequent adverse effects being nausea and vomiting related to the use of neuraxial opioids. Scoliosis may impair catheter introduction during continuous anesthetic techniques, being critical that this procedure is performed by experienced professionals 1,2,74.
Some CP patients may have delayed anesthetic recovery. This may be due to hypothermia, especially in patients with temperature regulation changes. Active heating device (such as forced air) should be used to normalize temperature. Other cause for delayed anesthetic recovery is the residual effect of volatile inhalational agents. MAC is decreased in CP patients being possible that awaken MAC is also decreased 1.
Postoperative sialorrhea may impair airways maintenance and frequent aspirations may be required. Careful attention should be given to protect airways in children with pseudobulbar paralysis for the possibility of excessive secretion, regurgitation and vomiting 1.
CP patients often have difficulties to cough, repetition respiratory infection and difficulty to eliminate secretions and benefit from postoperative chest physical therapy 1,2.
In patients submitted to long procedures, such as scoliosis correction, there may be postoperative respiratory complications. Continuous airway positive pressure may help preventing such complications. Occasionally, there might be the need for prolonged mechanical ventilation and tracheostomy is indicated 2.
Irritability during anesthetic recovery is common. Eliminating causes and excluding frequent etiologies, such as pain or urinary retention, may be difficult. Irritability may also be due to emergence in an unknown environment, especially for children with mental retardation. The presence of parents in the post-anesthetic recovery unit may be beneficial for the child. Visual and auditory abnormalities are also causes of postoperative irritability 1.
Anticonvulsants should be started as early as possible. This may be unfeasible for children with prescription of fast or those presenting nausea and vomiting. Several anticonvulsants, however, have a half-life of 24 to 36 hours and in adequate therapeutic levels, their withdrawal for 24 hours does not pose significant risk of seizures. Anticonvulsants, such as benzodiazepines, phenitoine and phenobarbital may be intravenously administered. Sodium valproate, carbamazepine and diazepam may be rectally administered although with variable absorption. It is more important to maintain anticonvulsants in children with history of generalized seizures than in those with partial seizures. The anesthesiologist, together with the assistant physician, should establish a therapeutic approach to prevent postoperative seizures 1.
Spasticity is often treated with baclofen or dantrolene. Abrupt baclofen withdrawal may lead to seizures and hallucinations. Rectal or intravenous diazepam (0.1 to 0.2 mg.kg-1) may be used until regular oral medication may be resumed. In case of spinal baclofen, medication should continue in the postoperative period. If the pump was removed, oral baclofen should be previously administered for 2 to 3 days, although being less effective that spinal baclofen 1.
Muscle contracture may impair positioning in the post-anesthetic recovery unit or ICU. When epidural analgesia is used to control postoperative pain, prolonged pressure of bone structures may lead to skin injury, especially in malnourished children 1.
Children under regional anesthesia may present compartmental syndrome due to the natural frequency of orthopedic procedures in lower limbs and to the inability to report pain. This syndrome is developed when there is increased compartmental space pressure, enough to impair tissue perfusion and risk the feasibility of existing structures (muscles, tendons, vessels and nerves). Internal causes (edema and hemorrhages), extrinsic compression (bandages) or plaster (pressing the limb) may cause the compartmental syndrome with pressure levels above 100 mmHg. The degree of the injury will depend on the speed in which pressure increases and its duration 75. This is particularly common after tibial osteotomy. Care should be taken with the plaster and raising the legs decreases the risk of this complication 1,2.
CP children are prone to constipation due to decreased motility, decreased fluid intake and changes in intestinal motility, which may be worsened by opioids. Laxants and enemas may be necessary.
Postoperative analgesia is a very important part of CP patients' management. Inadequate analgesia may lead to increased postoperative muscle tone and spasm with worsening of pain. Effective analgesia may prevent this cycle of events 1.
Pain may be very difficult to evaluate due to mental retardation or difficult verbal communications. Behavioral indicators, such as face changes, moaning, crying and sleep abnormalities may be present in painless situations, being difficult to interpret in those patients. Attempts have been made aiming at creating a pain scale based on behavioral indicators. Unfortunately all attempts were unable to safely evaluate validity and sensitivity of those scales 1.
Something interesting in CP children with severe developmental impairment is the possibility of indifference to pain, that is, they have a high pain threshold characterized by the lack of basic behaviors caused by manipulations, which are typically painful 1.
Postoperative pain should be separated from hunger, anxiety, discomfort due to position, as well as from headache, toothache, middle ear otitis, dysmenorrhea and gastroesophageal reflux 1.
Most frequent CP patient procedure is lower limbs orthopedic surgery. These patients often present severe postoperative muscle spasms, which cause severe pain and stress for children, parents and assistant physicians. Diazepam is effective to decrease muscle spasm with consequent pain relief, however it often leads to prolonged sedation 1.
In children submitted to lower limb orthopedic surgeries, lumbar epidural analgesia is extremely effective to control pain and, as a consequence, to prevent muscle spasm, which is in general due to medullary reflex triggered by pain. The association of local anesthetics and opioids promotes excellent analgesia, however there is the possibility of nausea and vomiting, especially when morphine is used, when patients are resistant to antiemetic therapy and in the presence of muscle spasm. When epidural morphine is used alone in intermittent doses there is a high incidence of sedation in cerebral palsy children 76. Local epidural anesthetic associated to epidural clonidine promotes excellent analgesia, major muscle spasm decrease and lower incidence of nausea and vomiting 2,77.
Caudal epidural anesthesia with opioids has been used with adequate postoperative analgesia and absence of significant adverse effects 78.
Selective dorsal rizothomy (posterior nervous roots resection between L2-S2) is associated to severe pain, muscle spasm and postoperative dysesthesia. Epidural and spinal morphine, associated or not to bupivacaine, have been used with adequate analgesia.
Intravenous morphine (20 to 40 µg.kg-1.h-1) and ketorolac (1 mg.kg-1), followed by intravenous 0.5 mg.kg-1 every 6 hours for 48 hours to control postoperative pain, associated to midazolam (10 to 30 mg.kg-1.h-1) to prevent muscle spasm, is an effective and safe technique for patients submitted to selective dorsal ryzothomy 14,60,77,79,81. Spinal morphine, in intermittent doses or continuous infusion associated to bupivacaine has been used for postoperative analgesia in this type of procedure. Results have shown lower pain scores with the association of opioids and local anesthetics in continuous infusion, without significant differences in the incidence of pruritus, muscle spasm and hemodynamic and ventilatory parameters as compared to intermittent opioid doses 82.
CP patients submitted to extensive surgical procedures and needing intravenous or epidural analgesic infusion, should be strictly monitored (blood pressure, respiratory rate, pulse oximetry) 1.
CHRONIC PAIN IN CEREBRAL PALSY
Recognizing the presence of chronic pain in CP children is difficult, especially in patients with speech problems. Pain location may be very difficult, often involving a process of eliminating common causes. This includes hip subluxation, gastroesophageal reflux, thoraco-lumbar pain secondary to scoliosis, arthritis and dysmenorrhea. Manipulating or palpating the potentially involved area1 may often locate pain.
Patients without mental retardation, especially adolescents, may present depression, which may be exacerbated by chronic pain 1.
A case of neuropathic pain after multiple orthopedic surgeries in cerebral palsy patient has been recently reported 83.
A multidisciplinary approach to treat chronic pain in these children is desirable 1.
Cerebral palsy patients are often submitted to surgical procedures due to primary disease or related cerebral palsy-induced situations. Anesthesiologists play an important role in decreasing anesthetic-surgical morbidity and mortality in CP patients. The understanding of the pathophysiology of different cerebral palsies, as well as of associated diseases and their therapies is critical because it allows anesthesiologists to anticipate and prevent intra and postoperative complications in these patients.
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Dr. Marcius Vinicius M. Maranhão
Address: Rua Manoel Bernardes, 134/702 Madalena
ZIP: 50710-350 City: Recife, PE
Submitted for publication
May 18, 2005
Accepted for publication July 19, 2005
* Received from Disciplina de Farmacologia do Instituto de Ciências Biológicas da Universidade de Pernambuco e Serviço de Anestesiologia do Hospital Universitário Oswaldo Cruz, Recife, PE