Disease of Childhood

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© Springer Nature Switzerland AG 2020
Craig Sims, Dana Weber and Chris Johnson (eds.) A Guide to Pediatric Anesthesiahttps://doi.org/10.1007/978-3-030-19246-4_12

12. Chronic Disease of Childhood

Alison Carlyle1   and Soo-Im Lim1  

Department of Anaesthesia and Pain Management, Perth Children’s Hospital, Nedlands, WA, Australia



Alison Carlyle (Corresponding author)


Soo-Im Lim


Cerebral palsy, anesthesia, analgesiaAnesthesia, rhabdomyolysisMalignant hyperthermiaAnesthesia mucopolysaccharidosisAnesthesia, Hunter Hurler syndromeAutism spectrum disorder and anesthesiaPerioperative management diabetes children

This chapter describes several important non-respiratory diseases that may affect anesthesia in children. Optimal anesthetic management of these children requires careful planning and a collaborative approach with the multidisciplinary teams involved in their care.

12.1 Cerebral Palsy

Cerebral Palsy (CP) is an umbrella term used to describe a spectrum of neurological motor disorders that can be associated with other conditions such as seizure disorders and intellectual impairment. Most children have increased muscle tone or spasticity in one of more muscle group or limb. A minority of children have ataxia or dystonia rather than spasticity. Cerebral palsy results from pathogenic insults to the developing brain in utero or in the post-natal period. These insults include intracerebral hemorrhage, genetic disorders, fetal infection such as rubella and CMV, pre-eclampsia, peri-partum hemorrhage and maternal hyperthyroidism. Extreme prematurity and low birth weight are important risk factors. Approximately 80% of cases develop antenatally with the remainder in the first 2 years of life. The incidence is 1–2.5/1000 live births in western countries and has remained steady with the increase in survival rates of premature infants.

These children present with a broad range in the severity of their symptoms. Some have an isolated limb spasticity and normal intellect, while others have severe spasticity, limb deformity and developmental delay. The Gross Motor Function Classification System (GMFCS) categorizes the severity into mild (level 1) to severe (level 5) based on the level of movement and activity a child can perform. Children with the severe GMFCS 5 level often have difficulty swallowing and feeding and may require nasogastric or gastrostomy feeds. Despite this, they often have weight loss and may have nutritional deficiencies, dehydration or anemia. Chronic low fluid intake coupled with pre-operative fasting may increase the risks of developing pre-renal renal failure.

Children with cerebral palsy require a multidisciplinary approach of community and hospital care. The aims are to improve mobility and posture by minimizing muscle contractures, spasticity and spasms, as well as controlling symptoms of accompanying disorders such as seizures and gastro-esophageal reflux with pulmonary aspiration. Management includes a combination of physical therapies, surgical procedures and medical treatments to reduce spasticity such as diazepam, baclofen, vigabatrin and botulinum toxin. Anesthesia is commonly required in these children for orthopedic or dental procedures, feeding gastrostomy, fundoplication and botulinum toxin injections.

Botulinum neurotoxin is derived from clostridium botulinum bacteria and blocks the release of acetyl choline at the neuromuscular junction. An intramuscular injection produces muscle weakness lasting between 2 and 6 months, with peak effects at 4 weeks post-procedure. Treatment involves injections into multiple muscles at regular intervals, improving function across the CP spectrum. In children with mild CP (GMFCS 1 and 2) it improves movement and gait, whilst in more severely affected children (GMFCS 4 and 5) it assists with supine positioning and basic quality-of-life care by preventing limb contractures. Systemic absorption and generalized weakness are extremely rare side effects.

12.1.1 Anesthesia Management

Cerebral palsy patients present a number of challenges (Table 12.1). Communication may be difficult because of developmental delay, and children with normal or delayed intellect may be anxious because of past hospital experiences. Parents are usually a reliable source of information about past medical history and previous anesthesia. Some children have mild respiratory failure requiring CPAP ventilation at home. Premedication is often worthwhile in this patient group, taking care to minimize the likelihood of respiratory side effects.

Table 12.1

Summary of important anesthetic issues in care of children with cerebral palsy

Key anesthetic issues in children with severe cerebral palsy

Anxious; communication may be difficult

Bulbar problems and poor swallowing of saliva; postop secretion clearance

Some are at risk of reflux and aspiration

Poor cough, frequent chest infections, kypho-scoliosis; risk of pneumonia or respiratory failure

Limb contractures; positioning for surgery may be difficult; pressure area risk

Altered thermoregulation and risk of hypothermia

Pain assessment difficult; painful muscle spasms after orthopedic surgery common

Pre-existing seizure disorder


Children with severe CP have many potential anesthetic problems depending on the procedure, but the most important are the potential postoperative respiratory complications and pain management issues.

Many of the children with severe cerebral palsy are at risk of reflux and aspiration, but unfortunately also often have very difficult venous access. In children who have not had multiple previous episodes of pulmonary aspiration, a careful inhalational induction is a reasonable approach. Although neck and jaw contractures can occur, airway management is usually straightforward. Suxamethonium does not cause rhabdomyolysis in children with cerebral palsy, but there is resistance to non-depolarizing muscle relaxants because of an up-regulation in the number of acetylcholine receptors. Nevertheless, a non-depolarizing relaxant would be used more often than suxamethonium for a rapid sequence induction. MAC values are reduced in the children most severely affected (GMFCS 4 and 5).

Positioning can be difficult as a result of limb contractures and spasticity. Great care must be taken to protect pressure areas and to avoid neuropraxia. Hypothermia is a significant problem. These children have abnormal thermoregulatory control and cool quickly as they have minimal subcutaneous fat and muscle mass and a high surface area to volume ratio. Active warming is needed even for short procedures.

12.1.2 Post-operative Care

Respiratory care and pain management are the major postoperative problems in children with severe cerebral palsy. These children often have a weak cough and diminished respiratory drive leading to sputum retention, atelectasis, chest infection and respiratory depression. Some may require a period of respiratory support or close observation in a high dependency area.

Pain can be difficult to assess in children with cerebral palsy, and input from their parents is useful to gauge the effectiveness of analgesia. Muscle spasms triggered by pain and anxiety are a particular problem in this patient group. They cause paroxysms of intense pain that can be difficult to prevent and treat. Post-operative analgesia is optimized using a combination of non-opioid analgesics, intravenous opioid infusion, epidural analgesia or other regional technique, and sometimes a ketamine infusion. Regional techniques are particularly useful in reducing spasms. Epidural clonidine helps reduce spasms and may produce mild sedation which is often useful in the early postoperative period. Intravenous opioid infusions are commonly used, but require caution in this vulnerable patient group who are at risk from cough suppression, sedation and respiratory depression.

12.2 Muscle Disease

Muscle diseases, or myopathies, are uncommon conditions that have important implications for anesthesia. There are three specific risks—the risk of rhabdomyolysis from suxamethonium in any child with a myopathy; the risk of rhabdomyolysis from volatile agents in a child with muscular dystrophy, and finally the risk of malignant hyperthermia (MH) in some children with rare, specific muscle disorders. With increasing age and progression of the disease, myopathies become multi-organ diseases affecting cardiac and pulmonary function.

Practice Point

Before anesthetizing a child with a known or suspected myopathy, consider the following:

  • Is the health care facility suitable?

  • Is there a risk of MH?

  • Is there a risk of rhabdomyolysis from volatile agents?

  • Is there a risk of metabolic acidosis from propofol anesthesia?

  • Are there cardiac or respiratory problems?

12.2.1 Categories of Muscle Disease

There are a large number of rare, eponymously named myopathies in children, but a simple classification of the more important ones with their specific anesthesia problems is listed in Table 12.2. Some myopathies have a causative or genetic link with MH, although there is variation within these, reflecting the rarity and complexity of the disease. As the child gets older, other consequences of the underlying muscle fiber problem become more apparent. Cardiac muscle is often affected, leading to arrhythmias, conduction defects and cardiomyopathy. Postural and mobility changes occur with limb deformities, contractures and scoliosis. Respiratory muscle weakness causes poor swallow and cough, a propensity to chest infection and respiratory failure. Developmental delay and seizures occur with some myopathies.

Table 12.2

Overview of specific anesthesia problems related to muscle diseases

Muscle disease

Specific concerns

All myopathies

Rhabdomyolysis with suxamethonium

Muscular dystrophies

Rhabdomyolysis with volatile agents

Cardio-respiratory problems later in life

Mitochondrial myopathies

Lactic acidosis with fasting

King Denborough

Central Core, Multi-Minicore, Centronuclear

Congenital myopathy with cores & rods

Nemaline rod

Congenital fiber type disproportion

KDS, idiopathic hyperCK-emia

Native American myopathy

Exercise induced rhabdomyolysis

Known association with MH

Based on Litman et al. Anesthesiology 2018;128: 159–67

12.2.2 Rhabdomyolysis with Suxamethonium

Every child with a muscle disorder is at risk of hyperkalemic cardiac arrest from suxamethonium, and it should not be used under any circumstances. Suxamethonium causes depolarization of the muscle cell membrane, causing a prolonged contraction of the abnormal muscle fiber with breakdown of the cell membrane and release of potassium. The breakdown of the muscle cell membrane destroys the muscle fiber and is called rhabdomyolysis. It is the depolarisation caused specifically by suxamethonium that is the problem, and non-depolarizing relaxants are safe to use.

Treatment of a suspected hyperkalemic cardiac arrest follows APLS guidelines but specific therapies to consider are calcium, sodium bicarbonate and dextrose-insulin. Resuscitation should continue until the plasma potassium has been normalized.


If laryngospasm occurs in a child with myopathy, suxamethonium cannot be used to treat it. Options are a bolus of propofol 3–5 mg/kg and a non-depolarizing relaxant. The dose of relaxant needed to relax the vocal cords is not known, but is likely to be small, such as 0.2 mg/kg atracurium or 0.2 mg/kg rocuronium (the latter could be antagonized with sugammadex).

12.2.3 Muscular Dystrophy (Duchenne and Becker )

The muscular dystrophies are characterized by the absence of dystrophin in the muscle fiber (including cardiac), making the sarcolemma unstable. They occur only in males. Asymptomatic female carriers have no specific risks with anesthesia. The disease usually presents during the first years of childhood, so there is small a group of yet-to-be diagnosed preschool boys with the condition. However, up to half of the children with muscular dystrophy have a positive family history. There were several deaths from rhabdomyolysis each year in the USA in this group of children when suxamethonium was routinely used for elective intubation.

Young children with muscular dystrophy are active and reasonably well but later develop multi-organ problems, most commonly during the teenage years. Limb contractures and scoliosis develop, and ventilatory failure progresses from respiratory muscle weakness and restrictive lung defects secondary to kyphoscoliosis. Autonomic dysfunction may occur, suggested by a resting tachycardia. Dysphagia results from weakness of striated muscle in the upper pharynx and smooth muscle of esophagus which can result in aspiration and passive regurgitation during anesthesia. Cardiomyopathy becomes more of a concern over the age of 10 years—30–50% of teenagers and 100% of 18 year olds have cardiomyopathy.


The muscular dystrophies are not associated with MH. The same triggers as MH may however, cause rhabdomyolysis and an MH-like clinical picture. Anesthesia for Children with Muscular Dystrophies

There are several problems with anesthesia in these children (Table 12.3). Suxamethonium is contra-indicated. Non-depolarizing relaxants can be used, but the block is likely to be more profound and longer lasting than usual.

Table 12.3

Anesthesia-related problems in children with Duchenne’s and Becker’s muscular dystrophy

Anesthesia-related problems in DMD and Becker’s

Dystrophinopathy with hyperkalemia from suxamethonium and probably volatiles

At risk of ventilatory failure from anesthesia and surgery in later childhood

Cardiomyopathy in later childhood

Dysphagia and pulmonary aspiration in later childhood


Avoid suxamethonium

Avoid volatile agents

Use propofol-remifentanil anesthesia and avoid muscle relaxants

Avoid post-op deterioration in respiratory function

Take precautions for cardiomyopathy and aspiration in older children

The safety of volatile anesthetic agents in these children is controversial. Volatile agents have been used without problems in the past, but there are regular case reports of them causing hyperkalemic cardiac arrest. Volatile agents probably trigger rhabdomyolysis under unknown predisposing factors, and their inconsistent effect has led to discussion about their safety in muscular dystrophy patients—most would completely avoid volatiles.

Practice Point

When presenting for anesthesia, young children with DMD have the problem of rhabdomyolysis with suxamethonium and volatiles; older children and adults also have the problems of cardiac and respiratory failure, and steroid dependency.

12.2.4 Malignant Hyperthermia

Malignant hyperthermia (MH) is a rare, inherited disorder of the skeletal muscle that predisposes to a life threatening hypermetabolic state after suxamethonium and volatile anesthetics. MH reactions are rare, but approximately half occur in children younger than 15 years. It is very rare in the first year of life, and an uneventful anesthetic in the past is meaningless. Most children at risk of MH are asymptomatic, with only a few myopathies known to be associated with an MH risk (Table 12.2). Diagnosis

Intraoperative MH causes a hypermetabolic state with lactic acidosis. Masseter muscle rigidity or spasm in response to suxamethonium may be the first sign, but is not specific to MH (see Chap. 2, Sect. 2.​9.​3). Early signs are increased CO2 production, tachycardia, and metabolic acidosis. Fever develops, but it is often a late sign. Subsequently, muscle cell membrane pumps fail and there is leakage of intracellular elements with hyperkalemia, myoglobinemia and disseminated intravascular coagulation. Rarely, MH may begin in the postoperative period, up to several hours after anesthesia. Management of a MH Reaction

A brief overview of management is listed in Table 12.4, but is more comprehensively covered in the guidelines from the Australian and New Zealand College of Anaesthetists and the Association of Anaesthetists in Great Britain and Ireland. The dose of dantrolene in children is the same as in adults, 2.5 mg/kg. There is no need to eliminate the anesthetic machine because the load of volatile agent in the patient will higher than that in the machine. High flow oxygen should be used though to wash-out the volatile from the patient and machine. The role of charcoal filters is still being determined.

Table 12.4

Overview of management of suspected MH reaction in children

Management of MH reaction

Call for help

Hyperventilate with 100% oxygen

Intravenous anesthesia if clinically appropriate.

Dantrolene 2.5 mg/kg and 1 mg/kg dose can be repeated to maximum of 10 mg/kg

Start active cooling to less than 39 °C

Treat arrhythmias, hyperkalemia, acidosis

Transfer to ICU for continuing treatment and monitoring MH Testing of Children

The in-vitro contracture test is the gold standard test for MH susceptibility. It is not usually performed in children under 10 years or 30 kg as they do not have an adequate thigh muscle from which to obtain a muscle sample. Genetic testing is used but not as a first-line test for index cases or their relatives. MH genetics remain heterogeneous and multiple mutations are likely to be involved, although a handful of mutations can definitely be characterized as MH causative. A negative genetic test does not rule out the disease. Management of a Child with a Family History of MH

Many children who present for anesthesia have a family history of an MH reaction, but their susceptibility is not certain as they cannot be tested. Children who should be considered particularly at risk are those where the reaction was in a close relative, or more than one relative in the family. The history of an MH reaction however, is often in a more distant relative. In this situation, a pragmatic approach is usually taken and the child treated as susceptible, even though the real risk is not known but likely to be low.

Fortunately, trigger-free anesthesia is simple to achieve in most circumstances. The principles are the same as in adults: propofol-based anesthesia, volatile-free equipment and avoidance of suxamethonium. Elective cases are scheduled first on the list—anesthesia workstations can take up to an hour to prepare and flush so their residual agent concentration is less than 5–10 parts per million. Activated charcoal filters can shorten this time. There are also alternatives to the machine preparation if the circle circuit and positive pressure ventilation are not needed. One alternative is to use a disposable T-piece circuit with oxygen from a wall source. Another is to use the machine’s common gas outlet, which can usually be prepared by flushing with oxygen at 10 L/min for 10 min.

Reactions after trigger-free anesthesia are rare. MH-susceptible children may be safely managed as day procedure cases with standard times for postoperative monitoring and care, although some units observe for fever for several hours before discharge. Like any other child undergoing anesthesia, these children are at risk of laryngospasm. Although a bolus of propofol is a reasonable first treatment, having a non-depolarizing relaxant drawn up and ready to use is wise in any child with a contraindication to suxamethonium.

12.2.5 Metabolic and Mitochondrial Myopathies

Disorders of fatty acid metabolism in the mitochondria affect muscle and other organs such as the brain and heart. This group of disorders is termed metabolic myopathies, or mitochondrial myopathies. These children present with neurological and muscle symptoms, cardiomyopathy, respiratory failure and metabolic disorders. Fasting may initiate fatty acid metabolism and trigger lactic acidosis, so the duration of fasting is minimized and IV fluids containing 2.5–5% glucose given. These children are considered at risk of developing propofol infusion syndrome at relatively low doses of propofol. An induction dose of propofol is safe, as is volatile anesthesia. Brief propofol-based anesthesia may also be safe, although there is debate about this technique in these children. Suxamethonium is contraindicated as with all myopathies.

12.2.6 Anesthesia for Muscle Biopsy

A muscle disorder might be suspected in infants who are hypotonic (‘floppy’) or have other clinical signs, and these infants might require anesthesia for muscle biopsy. Anesthetic management is tailored to the suspected diagnosis and any possible link to MH or propofol infusion syndrome, as well as any cardiac or respiratory problem. Apart from avoiding suxamethonium, many types of anesthesia have been used without apparent problem. If the child’s creatine kinase is elevated, it would seem reasonable to avoid volatile agents, and if the lactate level is elevated, minimize propofol anesthesia. Alternatives such as ketamine or regional techniques can also be considered.

12.3 Mucopolysaccharidoses (MPS)

This is a group of inborn errors of mucopolysaccharide (also known as glycosaminoglycans) metabolism. Mucopolysaccharides are long chain carbohydrates forming connective tissues and bones. An enzyme deficiency in the degradation pathway causes deposition of these molecules throughout the body. Hurler syndrome is the most severe form. The other mucopolysaccharidoses include Hunter, San Filippo and Morquio syndromes and share some or all of the Hurler characteristics in a somewhat milder form (Table 12.5). Patients with Hurler’s syndrome present early in infancy with hernias, macrocephaly, recurrent respiratory infections and limited hip abduction. These children gradually develop the characteristic features and complications over time as more mucopolysaccharides deposit in tissues, and developmental delay is apparent by 1 year of age. Stem cell transplant or enzyme replacement therapy is now available for many forms of mucopolysaccharidosis. If started at a young age, it improves long term outcome and reduces the severity of airway changes. It does not however prevent neurocognitive, cardiac valvular or skeletal changes.
Nov 27, 2021 | Posted by in ANESTHESIA | Comments Off on Disease of Childhood

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