[MIM 159 050, 300 376, 310 200]

(Myopathy of Duchenne de Boulogne, dystrophinopathy)

Prevalence: 1/3500 boys. Severe progressive myopathy by absence of dystrophin secondary to a mutation in the DMD gene. X-linked recessive transmission (Xp21.2) but a de novo mutation is observed in 30 % of cases.  The majority of women carrying the mutated gene are asymptomatic but 2.5% of them present with a clinical picture more or less similar to the boy's one. In addition, even in asymptomatic cases, some cardiac involvement is observed in 60-70% of the cases: abnormal ECG, dilatation of the left ventricle or cardiomyopathy. This cardiac involvement cannot be predicted from the maternal phenotype, the type of mutation, the presence of muscular symptoms, the age or the CPK blood level. Given the risk of cardiomyopathy (which sometimes requires a cardiac transplantation), regular cardiac monitoring is recommended for the mothers carrying a mutation in the DMD gene .

Clinical picture:

-         small child: pseudohypertrophy of the calves, Gowers maneuver to stand up, walking difficulties between the age of 8 and 10 years. CPK levels are 50 to 200 times higher than normal

-         adolescent: wheelchair-bound, scoliosis, swallowing difficulties, progressive respiratory insufficiency, biventricular hypertrophy, heart failure following dilated cardiomyopathy, atrioventricular conduction disorders. The echocardiographic signs appear in general at the age of 6 years and an annual assessment is recommended from the age of 10 years. Keep in mind that echocardiography at rest does not evaluate the myocardial response to surgical stress, change of position or tolerance of the positive pressure ventilation. Sinus tachycardia at rest is usually present.

Treatment: 

-         early corticotherapy (prednisone 0.75 mg/kg/day or deflazacort 0.9 mg/kg/day as initial dose) can slow the progression of the disease: the patient remains able of walking for an average of 3 more years, scoliosis progresses less rapidly (and a surgery can often be avoided) and cardiomyopathy evolves more slowly.

-        in case of nonsense mutation, ataluren (Translarna®) may be given orally (3 doses daily): this medication seems to circumvent the mutated codon and improve the production of dystrophin.

-        an annual echocardiography is recommended from the age of 6 years to quickly detect the first signs of cardiomyopathy and establish a treatment with an angiotensin-converting enzyme inhibitor and / or a β-blocker. Cardiac MRI should be preferred because it is more sensitive to measure the structure and the function of the myocardium, and the quality of echocardiography is quickly limited by chest deformation, scoliosis and respiratory insufficiency.

Cases of fatal fat emboli have been reported after minor trauma (falls without fractures) among adolescents suffering from Duchenne muscular dystrophy and receiving corticosteroid therapy: osteopenia, relative immobility, obesity and corticosteroids are contributing factors because they increase the fat content of the bones. This should be kept in mind in case of onset of respiratory distress and/or disorders of consciousness after a fall.

Anesthetic implications: 

-        EKG and cardiac echography: cardiomyopathy ?

-        assess preoperatively the effectiveness of cough

-         hypomotility of the digestive tract with gastric emptying time: consider as a full stomach and expect a postoperative ileus;

-         NO succinylcholine because there is a major risk of acute hyperkalemia by rhabdomyolysis; no increased risk of malignant hyperthermia but the absence of dystrophin causes structural and functional changes in the RYR1 muscle receptor involved in malignant hyperthermia: this increases the fragility of the muscle cell membrane and might explain the reaction to the administration of halogenated agents and or succinylcholine (AIR for Anesthesia-Induced Rhabdomyolysis, see below). Hyperkalemic cardiac arrest is the only indication for calcium administration in the most recent APLS recommendations. Moreover, due to the severe muscular lysis, ECMO and emergency hemofiltration may be necessary to save the patient.

-         the use of the halogenated is a matter of controversy: cases of rhabdomyolysis have been reported during or after using a halogenated agent, especially during childhood, when the muscles are regenerating. They should thus best be  avoided. However, in many cases halogenated agents have been used without problems: if necessary, prudent inhalation induction with sevoflurane is thus an option provided one is ready to treat cardiac arrest if it occurs and  stop its administration as soon as a venous access is secured.

-         propofol-based total intravenous anesthesia is the first choice, but the presence of cardiomyopathy can reduce the hemodynamic tolerance to it; it is also important to avoid systemic hypotension and assess the hemodynamic response to the change in position or ventilation mode

-        titrate the dose of non-depolarizing neuromuscular blocking drugs to effect: in general, the onset of action is slower and the duration of  action is prolonged, especially after the age of 9-10 years (walking difficulties)

-         given the fragility of the sarcolemma and the decrease in the metabolic capacity of mitochondria in these muscles, it is prudent to avoid any circumstance that could promote rhabdomyolysis: hypoxemia, acidosis, hypotension, hypoglycemia, agitation or chills during the awakening phase, NSAIDs (?); it is possible that the use of a halogenated agents destabilizes the sarcolemma and makes it more fragile in case of a second tissue trauma: the absence of agitation during awakening following TIVA could partially explain its protective effect.

-         intubation can be difficult, especially from the adolescence onward: macroglossia, small mouth opening, decrease in cervical spine mobility

-        in case of peripheral nerve blockade, the muscular response to nerve stimulation can be difficult or even impossible to obtain when significant fibrosis is present; if ultrasound guidance is used, the change in muscular echogenicity may make identification of nerve structures more difficult

-         in case of corticosteroids, cover the perioperative needs;

-         significant risk of post-anesthesia or post-sedation if the vital capacity is < 50% of normal; risk major if < 30%.

-         awakening: need for pressure-support ventilation  followed with non-invasive ventilation; gastric distension should  be prevented as well as postoperative ileus because they decrease diaphragmatic excursion.

-         postoperative thromboprophylaxis is necessary as soon as the patient's mobility is reduced

-         in carriers of a mutation of the DMD gene: preoperative ECG and echocardiography; in the absence of scientific data, it is probably wise and safe to avoid using halogenated agents and succinylcholine.

References : 

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Updated: February 2021