Recommendations for anesthesia in patients with collagen VI-related diseases

Pathology: Collagen VI deficiency myopathy
ICD 10: G71

Phenotype range:
Mild: Bethlem myopathy/benign congenital muscular dystrophy
Intermediate: cingulate muscular dystrophy/myosclerotic myopathy
Severe: Ullrich myopathy/atonic sclerotic congenital muscular dystrophy

The condition was first described by Ullrich in 1930 and by Bethlem in 1976, respectively. It is caused by mutations in any of the 3 genes coding for Collagen VI synthesis, COL6A1, COL6A2 and COL6A3. Collagen VI is one of the most important substances contributing to the stability of the extracellular matrix. The functionality of the amount of Collagen VI present determines the clinical severity of the disease. Viewed in the past as different entities, Bethlem and Ullrich myopathies are now regarded as two extreme poles in the spectrum of Collagen VI deficiency myopathy. Both inherited mutations (mostly autosomal recessive) and de novo mutations (mostly autosomal dominant) are possible, but the latter are more common. The frequency of both is estimated at about 1 in 100,000 births (data vary for subtypes). Diagnosis relies on muscle biopsy and muscle genetic analysis. There is no effective treatment.

Brief description of the disorder: In Bethlem myopathy, patients will experience moderate muscle weakness, peripheral joint laxity and proximal joint contractures. Onset of symptoms will occur in late childhood or adolescence. Mobility will decrease with the years but still tends to be present in later life. We have no reliable data on life expectancy. In general, the disease has a benign course. In Ullrich myopathy, muscle weakness and joint contractures appear from birth or during early childhood. Infants may show congenital dysplasia of the hips with extensive hypotonia, while young children may have difficulty climbing stairs. Although some patients are initially able to walk independently, most will be in a condition that requires the use of a wheelchair by early adolescence. The respiratory muscles are frequently affected, so hyperventilation may be required, either intermittently (during the night) or on a permanent basis. The clinical course is sometimes aggravated by recurrent lung infections. The phenotype will be characterised not only by hypermobility of the peripheral joints and contractures of the proximal joints, but also by scoliosis and kyphosis. Affected individuals may exhibit a round face with long, lean limbs and muscle wasting. Muscle weakness may also hinder proper chewing, leading the patient to be underweight. Collagen VI malfunction can also cause follicular hyperkeratosis, with slow healing and keloid scar formation. Collagen VI is not present in the central nervous system, which is why cognitive ability is not impaired. There is no sensory component. Cardiac function is apparently normal in Ullrich dystrophy. Data on Bethlem myopathy are conflicting, with some reports of sporadic cases of mild cardiomyopathy of uncertain relevance to anaesthesiology. Serum creatine kinase may be slightly elevated as a biochemical marker.

Typical surgical procedures: Surgical correction of musculoskeletal deformities, particularly spinal deformities – e.g. correction of scoliosis. Distractive osteotomy – insertion of growth prostheses. Loosening of contractures. Tracheostomy, gastrostomy and repair of decubitus injuries in severe cases. Scar repair surgery.

Types of anaesthesia: We have no data establishing the superiority of intravenous or volatile anaesthetics. Medical literature and pathophysiology do not indicate any connection with malignant hyperthermia. However, if the patient is immobilised, the use of depolarising muscle relaxants should be avoided. Little information is available in the literature regarding neuroaxial blocking and regional anaesthesia in these patients. The presence of scoliosis and/or kyphosis can represent a significant technical challenge. Regional anaesthesia may be advantageous in patients with impaired respiratory potential, but may also present significant challenges due to contractures and difficulties in positioning, as well as anatomical access. It should be noted that some reports indicate that even minimal tissue injury can trigger severe subcutaneous haemorrhage.

Indispensable additional (preoperative) diagnostic procedures: Respiratory function must be carefully assessed prior to the administration of any anaesthesia. Even more important than the chest X-ray are pulmonary function tests, which should be performed in order to assess any changes in the respiratory system. This also includes an arterial blood gas analysis. Although cardiac function may appear unimpaired in this disease, there may be some cases of right ventricular failure as a consequence of a prolonged respiratory effort, so an ECG and echocardiogram should be performed if any right ventricular problems are suspected. The significance of some sporadic reports of very mild and clinically irrelevant cardiomyopathy is still unclear. A blood test may reveal polycythaemia (respiratory system disorder) or a concomitant (airway/pulmonary) infection. Urea, creatinine and electrolytes will help to rule out any kidney or organ damage due to previous scoliosis and it will be helpful for the patient to undergo surgery in the prone position.

Special measures for airway management: In patients with typical facial stigmata, micrognathia and the presence of a high, arched palate, intubation difficulties may occur. Measures should be taken in the event of difficult airway management.

Special measures for transfusion or administration of blood products:There are no indications in the literature for additional measures required by myopathy per se. However, corrective spinal surgery and extensive musculoskeletal surgery entail procedural risks of increased blood loss.

Special measures for anticoagulation:We have no information on pathophysiology in relation to specific diseases. As already mentioned: procedural risks associated with complex musculoskeletal/spinal surgery should be borne in mind.

Special precautions for patient positioning, transport and mobilisation: Previous immobilisations, contractures and cases of underweight patients may be reported. Careful patient positioning is crucial to avoid decubitus ulcers, as well as nerve entrapment syndromes. This condition is associated with respiratory insufficiency and, while the prone position (for spinal surgery) may be useful for gas exchange, the problem of positioning requires careful evaluation. Ullrich myopathy is associated with follicular hyperkeratosis, which leads to keloid scar formation, slow healing and increased vulnerability of the skin and soft tissues. Special precaution is recommended with bandages, eye patches and other adhesive products.

Potential interaction between anaesthetics and the patient’s long-term medication: It may be that children with Ullrich myopathy are taking prophylactic antibiotics, which could affect the choice of antibiotics used for surgical prophylaxis. Cyclosporin A may be of benefit in the case of Ultrich myopathy, and it is possible that children given this drug will experience some side effects, including gingival hyperplasia and hypertension.

Anaesthetic procedure: Both inhalation and TIVA (total intravenous anaesthesia) techniques may be administered. We have limited data on the use of neuroaxial anaesthesia and regional anaesthesia. Invasive procedures may result in considerable skin and subcutaneous bleeding.

Special or additional monitoring: It appears that invasive arterial catheters are useful for assessing ventilation and gas exchange both during surgery and in the post-operative phase. In cases of pulmonary hypertension and/or right ventricular dysfunction, the application of advanced haemodynamic monitoring (Swan-Ganz catheter, Intra-operative TEE) should be considered.

Possible complications: Epidermal lesions and other reactions may occur from the use of bandages, eye patches and suction cups used to perform the ECG. Pressure sores may develop due to difficulty in positioning patients.

Post-operative care: In severe cases (typically in Ullrich dystrophy) respiratory failure may complicate the post-operative course. These patients should be treated in an appropriate environment, preferably in an intensive care unit.

Information regarding emergency situations/differential diagnoses … caused by the pathology, to provide a means of distinguishing between a possible side effect of the anaesthetic procedure and a manifestation of the pathology. Iatrogenic causes of respiratory failure should be avoided, including abuse of opioid analgesics, prolonged action of neuromuscular blocking drugs, hypothermia and residual anaesthetic agents.

Ambulatory anaesthesia: Due to the rare and complex nature of this condition and the risk of possible post-operative respiratory failure in patients with a severe form, ambulatory anaesthesia should only be used in milder phenotypes.

Obstetric anaesthesia: The literature does not provide data on parturient patients with Collagen VI deficiency myopathies. Neuroaxial procedures can be complicated by anatomical difficulties and epidermal or soft tissue vulnerability (haemorrhage!).

Source: OrphanAnestesia