Department of Anesthesiology - Residents Section

Anesthesia Knowledge - Marfan-Syndrome

Marfan-Syndrome

1. Genetics/Prevalence

Autosomal dominant disorder with high variability of clinical manifestation new mutation in 30% of cases.

» Varying degrees of clinical manifestation and high rate of new mutations (no family history) account for a surprisingly high rate of undiagnosed cases that often present with a catastrophic complication prevalence: 1:10,000, in all races/ethnic groups.

2. Etiology

Mutation in the FBN1-gene that encodes fibrillin-1, fibrillin-1 is a major constituent of microfibrils which in turn are components of the extracellular matrix, there functions are numerous, for instance they form elastic fibers together with elastin genetic diagnosis can be difficult because FBN1 is a very large gene and there are a number of other mutations on that gene that cause connective tissue disease (familial aortic aneurysm, autosomal dominant ectopia lentis), only if there are alive cooperative family members the mutation can be determined and and can be used for presymptomatic and prenatal diagnosis.

» The diagnosis is still primarily clinical.

3. Extracardiac manifestations

Tall, disproportionate stature with extremely long limbs and digits.

Pectus excavatum or pectus carinatum.

» This may have implications for cardiovascular surgery as these deformities might impair access to the heart through median sterniotomy, in elective aortic repair it may be beneficial to correct these deformities a few months ahead of time, simultaneous cardiovascular and sternal repair is not recommended because it may prolong the total duration of surgery excessively and bleeding from the bony surfaces may be considerable in light of anticoagulation during bypass.

Scoliosis, flat feet, asthenic habitus due to poor muscle development.

Lens dislocation, myopia, strabism.

Pneumothorax due to blebs.

Dural ectasia: abnormal stretching of the dura in the lumbar region producing a sac of dura and occasionally an anterior meningiocele that can cause radicular pain and neuropathy.

4. Cardiac manifestations

» Mitral valve involvement is typical for the child with Marfan's syndrome whereas aortic root involvement is progressive and typically affects the adult.

MVP: more common in female patients, progression of mitral regurgitation in on quarter of patients (higher rate than in general population with MVP) the treatment for mitral regurgitation in the patient with Marfan-syndrome is not different than from other mitral regurgitation.

Aortic root dilatation: often sinuses of Valsalva are dilated at birth but the rate of progression varies greatly between patients. Typically progression is slow (millimeters per year) and can be monitored with echocardiography the dilatation is almost always limited to the proximal part of the ascending aorta the aortic root diameter corresponds directly with the risk for development of aortic regurgitation with increasing root diameter the risk for aortic dissection increases but this association is not as clear as with the development of aortic regurgitation.

Dissection often involves the entire aorta beyond the bifurcation, also occlusion of the coronary ostia can occur (leading to sudden death), pericardial tamponade develops if there is retrograde dissection, dissection is rarely survived however, both aortic regurgitation and aortic dissection are rare at aortic root diameters below 50 mm, therefore 50 mm serves as a criterion for performing elective surgery, ideally the operation is performed before aortic regurgitation has developed and can be limited to aortic root replacement while the native aortic valve is preserved (especially in woman of childbearing age in whom anticoagulation necessary for prosthetic valves is contraindicated during pregnancy)

Classification of dissections:

5. Anesthesia considerations

Preoperative management:

Blood pressure control is the central component of preoperative management in either elective or emergency surgery. In elective cases for aortic root repair with or without valve replacement BP control is necessary to prevent dissection. In emergency surgery most often dissection has already occurred and BP control is mandatory to prevent progression of dissection.

To reduce shear forces on the aortic wall it is not only necessary to control BP but to reduce the rate of arterial pulse increase _P/_t or dP/dt (which is a direct reflection of contractility) pharmacological management:

?-blocker: Esmolol (as drip), Labetolol, Metoprolol or Atenolol if contraindications such as pulmonary hyperactivity exist, ?-blockers are the mainstay of management because they decrease contractility thus decreasing dP/dt thus decreasing shear forces on the aortic wall
Trimetaphan: if heart block or CHF are present (prohibiting the use of ?-blockers), it decreases BP and dP/dt but is more difficult to titrate and has numerous side effects (respiratory depression, nausea, urinary retention)
Nitroprusside: for BP-control only concomitant with _-blockers since alone it may increase dP/dt
Nitroglycerin: often used initially if patient presents with chest pain, once the diagnosis of dissection is made _-blocker should be added immediately
in the case of refractory hypertension one should consider the possibility of excessive renin- synthesis due to an intimal flap obstructing the renal arteries, ACE-inhibitors may have to be added to the regimen

Hypotension: most likely due to pericardial tamponade or frank rupture with hemorrhage

fluid resuscitation
vasoactive drugs
pericardiocentesis if pericardial tamponade is present and medical treatment fails (it has to be kept in mind though that pericardiocentesis can be counterproductive as the drainage of blood from the pericardial space may decompress the communicating channel between the aneurysm and the pericardial space which can lead to fatal recurrent pericardial tamponade) (see Isselbacher et al Circulation 90 2375, 1994)
one has to be aware of the possibility of "pseudohypotension" when an intimal flap or the aneurysm itself obstructs or compresses the lumen of a branch of the aorta (namely the subclavian arteries - where blood pressure is often measured), since there may be actually hypertension present treatment of presumed hypotension would be detrimental

Intraoperative management:

invasive monitors and management as in all CPB-cases
blood pressure control
special considerations for CPB:
- in most CPB cases the aortic canula is inserted into the root of the aorta, in patients with Marfan-Syndrome that is not possible because the root of the aorta is diseased and in cases where there is aortic dilatation without dissection the main objective of the procedure is to replace exactly that part
- an arterial canula can be inserted into the femoral artery while the cross clamp is applied between the end of the aneurysmatic portion of the aorta and the innominate artery, perfusion occurs retrograde from the femoral artery via the abdominal aorta, perfusion can be accomplished just as sufficient as when the arterial canula is in the ascending aorta
- it is possible that small size of the femoral artery presents a problem for placing the arterial canula
- if the aortic arch is involved (as it may happen if dissection occurs) circulatory arrest is necessary however that is true only if both the innominate and the left subclavian artery lie in the dissected area because cerebral perfusion can be maintained by one carotid artery provided there is no significant stenosis in the left carotid artery, perfusion occurs in a similar way as in cases where involvement is confined to the aortic root only the cross clamp would be placed more distally (but obviously proximal to the left carotid artery)

In Marfan Syndrome circulatory arrest is usually not necessary if repair of the dilated aortic root is performed (dilatation is usually confined to the root and does not extend into the branches of the arch), if dissection occurs, it can progress over the entire length of the aorta also involving the branches of the arch.