Case

Several decades ago, a 6-year-old girl, weighing 22 kg, was scheduled for adenotomy. With maternal presence, smooth anaesthesia induction was achieved with halothane and nitrous oxide. Venous access initially failed and, in the presence of a completely flaccid patient, the idea of endotracheal intubation without neuromuscular blockade came up. However, it was refused as being against the institutional policy. Venous access was ultimately successful and 30 mg (1.4 mg/kg) succinylcholine preceded by atropine 0.25 mg was injected. However, laryngoscopy was impossible, because of massive masseter rigidity. The anaesthetist called the supervising attending and mentioned malignant hyperthermia or myotonia as possible diagnoses. This was questioned by the attending, who proposed a second dose of succinylcholine. Finally, with some force, the trachea was successfully intubated.

The anaesthetist immediately requested a thermometer, which was not routinely available in theatre in those days, but the patient’s legs felt as if they were made of wood when the nurse attempted to insert the rectal probe. Almost simultaneously, ventricular arrhythmias appeared at a heart rate of around 140 beats per minute. Malignant hyperthermia was now accepted by all team members as the presumptive diagnosis. The minute volume was increased and halothane was turned off. Fentanyl, droperidol and pancuronium were given. Dantrolene was requested and then given in a dose of 20 mg. An arterial blood sample taken at 10 minutes showed a metabolic acidosis and an already elevated creatine kinase (Table 7.1). Following two doses of 1.25 mg verapamil the arrhythmias disappeared and the heart rate gradually came down, the body temperature never rose, but fell from 36.8 °C to 36.0 °C. Two hours later adenotomy was performed. Then, once extubated, the girl voided a large quantity of reddish-brown urine. Because of shivering and peripheral cyanosis a second dose of 20 mg dantrolene was given.

Over the following hours, the body temperature rose to 38.5 °C, and after 24 hours creatine kinase peaked at 79 000 U/l. The girl suffered from transient muscle weakness and was discharged 2 weeks later with a letter stating the diagnosis of malignant hyperthermia.

Discussion

This case illustrates that malignant hyperthermia (MH) is an ever-present threat. Following a halothane induction, succinylcholine was a fulminant trigger for MH, initially presenting with masseter spasm, tachycardia and arrhythmias, followed by general muscle rigidity and rhabdomyolysis. With early treatment, cold infusions and exposure of the patient, an increase in body temperature could be prevented and was only seen later on the paediatric intensive care unit (PICU). Typically these patients, like the one described here, have no noticeable abnormal phenotype, and creatine kinase values are within a normal range. Only four well-defined neuromuscular disorders are considered to be related with MH susceptibility (Klingler et al. 2009). These are central core disease, multi-minicore disease, nemaline rod myopathy and King–Denborough syndrome. The molecular basis of MH susceptibility is in most cases a mutation at the ryanodine-1 receptor (RYR1) gene located on chromosome 19, causing an uncontrolled release of intracellular calcium from the sarcoplasmic reticulum that induces a hypermetabolic state (Rosenberg et al. 2015). The elevated risk for rhabdomyolysis, e.g. in Duchenne muscular dystrophy (Veyckemans 2010), and the risk for a myotonic reaction in myotonia congenita (Parness et al. 2009) are different entities (Schieren et al. 2017).

The diagnosis is based on the in vitro contracture induced by halothane and caffeine in freshly biopsied muscle tissue. In addition, today, molecular genetic methods allow spotting mutations at the RYR1 gene. Therefore, when a mutation is found, a blood test allows a patient to be identified as at risk for developing a MH crisis. However, to exclude MH susceptibility, muscle biopsy is still needed, because it is likely that not all mutations are already known. Clinically many fewer cases are observed than one would expect, given the autosomal inheritance and the fact that genetically MH susceptibility may be as common as 1:3000. This phenomenon is poorly understood, as is the clear male predominance.

Modern management of an MH crisis is substantially different from the treatment used at the time of the case described here (Glahn et al. 2010). Today, the initial dose of dantrolene would have been 2.5 mg/kg, a dose that has been shown to stop an MH crisis; further dantrolene can be given up to a maximum of 10 mg/kg. Activated charcoal filters would probably have been applied at the inspiratory and the expiratory limbs of the circle. Exchanging the anaesthesia ventilator is no longer recommended. Laboratory investigation would have been made more often and at systematic time points, e.g. at the time of first suspicion, and then at 30 minutes, 4 hours, 12 hours and 24 hours, with a special focus on blood gas, lactate, potassium and myoglobin. It is likely that surgery would have been cancelled. Modern fluid therapy would have avoided the development of hyponatraemia with a sodium concentration of 128 mmol/l. Hyponatraemia was commonly seen in those days, when hypotonic solutions were routinely given during anaesthesia.

This charming patient accompanied the author through his whole professional life. Around a decade later, malignant hyperthermia testing became available in Switzerland. The family was contacted, and surprisingly the mother, who had experienced multiple uneventful anaesthetics in the 1970s, was found to be MH susceptible by muscle contracture testing. This is not an uncommon story; more than half of MH episodes are preceded by one or even several uneventful anaesthetics, and only 6.5% of the patients have a positive family history (Larach et al. 2010). Later, after molecular genetic workup, the responsible mutation was identified in this family, and when our patient gave birth to a son, the mutation was identified in the umbilical cord blood of the offspring (Girard et al. 2006).

Later in life, this patient had several uneventful anaesthetics. When so-called ‘trigger-free anaesthesia’ is used, this means the avoidance of halogenated agents and succinylcholine, and a workplace that is adequately prepared (Cottron et al. 2014); the risk of an MH crisis is then abolished, and these patients can be treated and monitored as normal patients (Barnes et al. 2015).

Summary and Recommendations

Malignant hyperthermia (MH) is still with us, and every anaesthetist should be prepared to recognize the early signs of an MH episode.

Early treatment is crucial and dantrolene must be available. With timely treatment, an increase in body temperature may even be avoided altogether.

With ‘trigger-free anaesthesia’ these patients can be treated as normal patients. However, the workplace has to be adequately prepared.

Case

Decades ago, a 14-year-old boy with Charcot–Marie–Tooth disease was scheduled for revision of the nail of the big toe because of chronic pain. After an inhalational induction, anaesthesia was maintained with sevoflurane in air and oxygen. For postoperative analgesia a toe block was performed with bupivacaine 0.75% using a 24G needle, and diclofenac was given. Primary surgery included partial removal of the nail, using the Kocher (or Emmert) procedure.

Despite an apparently functioning nerve block during surgery, postoperative pain was a major issue, even requiring opioid medication. Over the next few years repeated surgeries were performed. Severe postoperative pain and protracted healing occurred each time. In view of the underlying disease, the parents questioned the indication for the application of local anaesthetics, and their potential toxicity.

Discussion

This case of a child with a neuromuscular disease, an inherited peripheral neuropathy, provides an opportunity to emphasize several educational points.

First, the classification of neuromuscular diseases can be done according to the primary anatomical target: e.g. brain, spinal cord, nerve roots, peripheral nerve, neuromuscular junction or muscle cell. Charcot–Marie–Tooth (CMT) disease involves the peripheral nerves; it is most often an autosomal dominant inherited motor and sensory peripheral neuropathy, but a genetic heterogeneity of CMT exists. The onset of symptoms occurs usually around adolescence; however, as in this case, onset in childhood can also occur. In addition to muscle wasting and sensory loss, CMT can be associated with relevant extremity pain. Distal orthopaedic procedures, especially foot surgery to improve walking ability, are quite common in these patients. Over the later course of the disease, because of muscular weakness, a high risk of perioperative pulmonary complications is the predominant problem.

Second, local anaesthetics are not generally contraindicated in patients with neuromuscular disease (McSwain et al. 2014). Regional anaesthesia may even be a preferred technique, e.g. in patients at a high risk for pulmonary complications such as with myasthenia gravis (Kocum et al. 2007) or myotonic dystrophy (Tobias 1995). The author remembers a schoolboy with myotonic dystrophy who could be perfectly managed with a spinal block for orthopaedic surgery (Fig. 7.2). In patients with CMT disease, central neuraxial (Schmitt et al. 2004) as well as peripheral conduction blocks (Schmitt et al. 2014) have been used without any reports of neurologic deterioration. No information is available, however, about small peripheral nerves which are ‘bathed’ in a local anaesthetic solution, as was the case in this patient with a toe block. Maybe these nerves are more vulnerable in the presence of pre-existing demyelinization and axon loss. In any case, a careful discussion with parents and patient about the risks and benefits of such a procedure is needed.

Figure 7.2 A child with myotonic dystrophy presenting for orthopaedic surgery.

Third, in the context of neuromuscular diseases the use of muscle relaxants is of special interest. Succinylcholine can cause hyperkalaemia in patients with extensive paresis, e.g. paraplegia or Guillain–Barré disease; in children with Duchenne disease it triggers rhabdomyolysis (cf. Case 5.2). In patients with myotonic dystrophy or myotonia congenita a generalized myotonic reaction is feared, and succinylcholine is contraindicated too. Malignant hyperthermia (MH) is rarely a problem; only four well-defined entities are at an increased risk for MH (cf. Case 7.1). With non-depolarizing relaxants an altered sensibility and the risk of residual paralysis should be considered; e.g. in children with Duchenne disease (Muenster et al. 2006). Especially in children with pronounced muscle weakness, even minimal residual paralysis can be fatal; the use of rocuronium followed by sugammadex is nowadays established and even becoming the gold standard in such situations (Tobias 2017).

Fourth, in some diseases it is not only the neuromuscular system that is affected, but also other organs, such as the heart or the gastrointestinal tract (Veyckemans & Scholtes 2013). In particular, patients with myotonic dystrophy and Duchenne disease are at a high risk of cardiac complications.

Summary and Recommendations

This case of a child with Charcot–Marie–Tooth (CMT) disease illustrates that even if the literature does not provide any information about neurologic sequelae after regional anaesthesia, a careful risk–benefit analysis has to be made on an individual basis.

The use of rocuronium followed by sugammadex combines the benefits of a profound blockade during intubation and surgery with the absence of any residual paralysis after the intervention.

Case

Many decades ago, a 6-year-old girl with Down syndrome, weighing 28 kg, was scheduled for dental treatment. The history included repair of a ventricular septum defect at the age of 2 years and several attacks of ‘asthma’ which apparently responded to classic treatment. Anaesthesia was induced with etomidate, succinylcholine and halothane. Nasotracheal intubation with a size 6.0 uncuffed tube failed. Smaller tubes were tried, but finally only a size 3.0 uncuffed tube could be inserted orally, and no leak was present. After consultation with an ENT specialist the decision was made to postpone the intervention and to proceed to tracheotomy on the dental chair.

The girl was transferred to the paediatric intensive care unit (PICU). Tracheoscopy showed an almost circular subglottic stenosis which was seen as a sequela of cardiac surgery with prolonged postoperative ventilation. Consequently a laser resection of the stenosis was performed and a Montgomery T-tube was inserted to keep the lumen open. The patient, initially scheduled for outpatient dental treatment, stayed in hospital for over 3 months; during this stay the dental treatment was performed. The patient was discharged with the T-tube in situ. Many weeks later decannulation was successful and the further course was uneventful.

Discussion

This case of a girl with Down syndrome and unrecognized subglottic stenosis illustrates that symptoms of a disease are often not recognized in children who are ‘special’ and do not pass the normal steps of development as usual. It is very likely that the ‘asthma’ attacks represented the airway restriction caused by the stenosis, and that the reduced activity, or limited exercise tolerance, was related to the presence of Down syndrome and the previous cardiac surgery. Similar cases have been reported in the literature (Farrow & Guruswamy 2008). Syndromic children are always more likely to have an unrecognized pathology.

Down syndrome is associated with a variety of pathologies (Lewanda et al. 2016) putting these patients at an increased risk of perioperative complications (Borland et al. 2004), e.g. bradycardia, post-extubation stridor and airway obstruction. Also, postoperatively, there is a higher risk of respiratory depression (Jay et al. 2017); this is probably related to the difficulty in finding the correct dose and not to real pharmacokinetic or pharmacodynamic differences. The author remembers a fatality, many decades ago, in a child with Down syndrome who was on a morphine infusion 2 days after cleft palate repair.

Congenital heart disease is common in children with Down syndrome; but gastrointestinal malformations, e.g. duodenal atresia, and other conditions such as Hirschsprung disease and cleft palate are more common too. Malformations of the cardiovascular system are present in more than one-third of children with Down syndrome; the most common finding is an atrioventricular septal defect, as in our patient. A typical finding is bradycardia during a sevoflurane induction which is unrelated to hypoxaemia or overdose. The origin and significance of the phenomenon are still unclear, although it seems to be transient and is usually no longer present during maintenance. It was the author’s practice just to observe bradycardia and not to treat it, because at the time of airway insertion it usually disappeared. Bradycardia was first mentioned in case reports (Roodman et al. 2003) and then systematically evaluated (Kraemer et al. 2010). Dexmedetomidine, which is known to cause bradycardia, can be given for sedation without an exaggerated risk (Miller et al. 2017). It is anyway an attractive choice in the view of the high incidence of airway obstruction and obstructive sleep apnoea in this population. Pulmonary hypertension is more common in children with Down syndrome and poses a major risk factor for general anaesthesia.

Children with Down syndrome typically have airway problems, not only obstructive sleep apnoea but also subglottic stenosis and other pathologies (Hamilton et al. 2016). They typically have smaller airway dimensions, and at the time when uncuffed tubes were exclusively used, it was recommended to start by using an endotracheal tube two sizes smaller than predicted by the age of the patient (Shott 2000). Today, for many routine interventions, all these considerations can be bypassed by using a laryngeal mask airway. Obstructive sleep apnoea is a very common feature; midface hypoplasia, pharyngeal muscle hypotonia, small airway dimensions combined with a relatively large tongue, obesity, increased secretions and common infections all contribute to the difficulties.

Craniocervical instability has a high incidence of up to over 60% in patients with Down syndrome; it involves the occiput–C1 level and more commonly the C1–C2 (atlantoaxial) level and is mostly seen in the context of generalized ligamentous laxity (Hata & Todd 2005). Forceful laryngoscopy and prolonged surgery with the head in the non-neutral position may put the patient at risk of a spinal cord injury. A preoperative radiographic screening in all patients with Down syndrome to exclude craniocervical instability is not realistic, and not requested by the majority of paediatric anaesthetists; every year thousands of such patients undergo anaesthesia without any problem. In symptomatic patients, however, further investigations and specialist advice should be requested. Chronic craniocervical instability can lead to a cervical myelopathy. The author remembers a 12-year-old girl whose ability to ambulate worsened over time despite corrective foot surgery, and who finally presented with a cervical myelopathy (Fig. 7.3).

Figure 7.3 A MRI showing severe cervical myelopathy as a consequence of atlantoaxial instability in a 12-year-old girl.

Especially in the neonate with Down syndrome the haematological peculiarities have to be known. Neutrophilia is very common, and up to 10% have a transient myeloproliferative disorder. Polycythaemia and thrombocytopenia are additional features.

Children with Down syndrome present a challenge for the paediatric anaesthetist because of the associated pathologies and the sometimes reduced cooperation in association with reduced intellectual capacity. It has to be emphasized, however, that children with Down syndrome are the sunshine in a paediatric hospital, and almost all of them are loved by their caregivers because of their amiability.

Summary and Recommendations

Children with Down syndrome often have multiple associated pathologies; some of them may be unknown at the time of anaesthesia, as was the airway stenosis in this case.

Difficulties in airway management and the high likelihood of postoperative airway obstruction have to be anticipated.

The anaesthetist must be aware of the high incidence of congenital heart disease and the occurrence of transient bradycardia during sevoflurane induction.