Mucopolysaccharidoses (MPSs) are a group of uncommon genetic diseases of connective tissue metabolism. It is well established that the elective treatment of subjects affected by MPS is multidisciplinary and must be carried out by experienced personnel in highly specialist centers. However, there is the possibility to perform an anesthesia in a peripheral center, where anesthesiologists might not have a large experience of MPS. Various attempts to produce guidelines have been made for MPS. There has been an increasing interest in the topic as it is demonstrated by the number of scientific studies published in the last few years (peak in 2011). We want to provide a summary of anesthetic management, reviewing the current literature on the topic in a procedural algorithm for these high-risk patients, who require surgical procedures and diagnostic examinations under sedation with a higher frequency than the general population.
The necessity of codified and univocal guidelines, suitable for all patients, is a common challenge in the field of rare diseases. The first difficulty arises from the lack of cases to study, so as to identify without excessive variety the clinical features of the conditions in study and from the consequent poor literature and the differences between worldwide centers in diagnosis, treatment, and management protocols. Various attempts to produce guidelines of this kind have been made for mucopolysaccharidoses (MPSs). There has been an increasing interest in the topic as it is demonstrated by the number of scientific studies published in the last few years (peak in 2011). It is well established that the elective treatment for subjects affected by MPS is multidisciplinary and must be carried out by experienced personnel in highly specialized centers. However, there is the possibility to perform an anesthesia for these kinds of pediatric patients in a peripheral center, where anesthesiologists might not have a large experience of MPS.
Our intent is to review the current literature on this topic in a procedural algorithm of anesthetic management for these high-risk patients, requiring surgical procedures and diagnostic examinations under sedation with a higher frequency than the general population. Particularly, we are focusing on perioperative (pre-, intra-, and post-) anesthetic management. Our final aim is to improve the quality of care offered and, as a consequence, the quality of life of subjects affected by MPS.
Mucopolysaccharidoses are uncommon [
The lack or deficiency of specific lysosomal enzymes leads to the storage of partially degraded glycosaminoglycans (GAG: dermatan sulphate, heparan sulphate, or keratan sulphate) [
Classification of MPS disorders includes 7 major types (I–IX) on the basis of clinical features, age at presentation, and biochemical alterations (Table
Classification of mucopolysaccharidoses.
Type | Denomination | Main clinical features | GAGS* | Enzyme deficiency |
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MPS IH | Hurler syndrome | Severe phenotype, macrocephaly, macroglossia, facial coarseness, hydrocephalus, mental retardation, joint stiffness, thoracic and lumbar kyphosis, possible odontoid hypoplasia. | DS, HS |
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MPS IS | Scheie syndrome | Joint stiffness, corneal turbidity, aortic valve disease, normal intellectual capabilities, macroglossia, normal stature, living until adulthood. | DS, HS |
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MPS I H/S | Hurler-Scheie syndrome | Intermediate phenotype, macrocephaly, macroglossia, joint limitations. | DS, HS |
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MPS II | Hunter Syndrome | Severe course MPS I H-like, moderate course-clinical intermediate phenotype, late manifestations, living until adulthood with or without mental retardation. | DS, HS | Iduronate-2-sulfatase |
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MPS III A | SanfilippoA syndrome | Behavior disorders, aggressiveness. | HS | Heparan-N-sulfatase |
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MPS III B | SanfilippoB syndrome | Progressive dementia, living until the second and third decade. | HS |
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MPS III C | SanfilippoC syndrome | Remarkable interfamilial variability, mild dimorphism. | HS | AcetylCoA:a-glucosaminide |
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MPS III D | SanfilippoD syndrome | Rough hair, limpid cornea, usually normal height. | HS | N-acetilglucosamine-6-solfatase |
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MPS IV A | MorquioA syndrome | Short trunk dwarfism, thin corneal opacities, skeletal dysplasia and spondylo epiphyseal, final height under 125 cm. | KS | N-acetilglucosamine-6-solfatase |
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MPS IV B | MorquioB syndrome | Idem MPS IV A, adulthood height under 120 cm. | KS |
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MPS VI | Maroteaux-Lamy syndrome | Hurler phenotype with pronounced corneal opacities and normal intellectual capabilities. | DS | N-acetylgalactosamine 4-sulfatase |
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MPS VII | Sly syndrome | High phenotypic variability, dense granulocyte inclusions, macrocephaly, possible odontoid hypoplasia, shortness. | CS, DS, HS |
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The MPS group includes a wide range of clinical manifestations with differences in life span and quality of life. All types are autosomal recessive inherited [
In spite of the severity of their somatic presentation types, IV and VI have no mental impairment [
MPS subjects require frequent surgical and diagnostic anesthetic procedures or sedations. They are common operations, including herniorrhaphy, adenotonsillectomy, and median nerve decompression; on the other hand, others demand nonroutine procedures such as cardiac valve replacement, spinal cord decompression, ventricular peritoneum shunt, and orthopedic surgery to rectify deformations and skeletal defects [
Main associated clinical conditions and possible treatment.
Associated medical conditions | Surgical clinical conditions |
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Mental retardation |
Communicating hydrocephalous |
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Seizures (MPSI, MPSII) [ |
Spinal cord compression |
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Joint stiffness |
Skeletal deformities: kyphoscoliosis, valgus and varus limbs, and carpal tunnel |
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Glaucoma |
Corneal opacity |
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Retina degeneration |
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Sensor neural deafness |
Chronic catarrhal otitis |
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Obstructive sleep apnea (OSA) |
OSA |
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Restrictive pneumopathy |
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Systemic arterial blood hypertension |
mitral-aortic stenosis failure |
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Abdominal wall hernia( |
Every MPS type is characterized by progressive craniofacial, articular, and skeletal deformities, cardiac involvement, and early death due to pulmonary infections or heart failure, often before adulthood (Table
Involvement of organs and systems.
Clinical manifestations | |
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Upper airways | Facial coarseness, hypertelorism, sunken nasal dorsum, anteverted nostrils, thickened lips, gingival hyperplasia [ |
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Lower airways | Expanded larynx and tracheobronchomalacia [ |
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Cardiac | Valvular disease, cardiomyopathy, right ventricular dysfunction and congestive heart failure [ |
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Orthopedic-Bone Changes | Short neck, joints stiffness [ |
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Others | Mental retardation [ |
Patients usually look normal at their birth but progressively develop clinical manifestations according to the kind of syndrome they are affected by [
The management of these situations is a challenge for the anesthesiologist. The anesthetic risk of MPS patients must be considered high for many reasons, including airway abnormalities, orthopedic deformities, pulmonary predisposition, and cardiac and neurological involvement (Table
Anesthetic risk: levels and causes.
MPS | Risk level | Multisystem impairment |
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I H (Hurler) [ |
Very high |
(i) Tendency to obstruction of the upper airway |
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I S (Scheie) [ |
Mildly high |
(i) Typical problems of I H (I HS) |
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III (Sanfilippo) [ |
Generally not increased | |
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IV (Morquio) [ |
Very high | (i) Odontoid hypoplasia |
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VI (Maroteaux-Lamy) [ |
High | (i) Cardiomyopathy |
Operative risk is higher in I, II, IV, and VI types (overall mortality rate is 20%) [
Algorithm of patients with MPS. ABG analysis: arterial blood gas analysis; PFT: pulmonary function test; MRI: magnetic resonance imaging; CT: computed tomography; CBC: complete blood count; ECG: electrocardiogram; Echo: echocardiogram; AVIL: angled video intubation laryngoscope; LMA: laryngeal mask airway; CPAP: continuous positive airway pressure; BiPAP: Bi-level positive airway pressure.
Standard preoperative preparation for an MPS subject is insufficient and ineffective. A full overview of every single case must be taken for a successful execution of the anesthetic procedure. In fact, the recurrence of deaths related to anesthesia in such patients is increased versus the general population.
In particular, the anesthesiologist must deal with three main concerns in such situations: difficult intubation, chronic pulmonary disease, dangerous neck manipulation for cervical instability [
Preoperative planning can be considered the most important part of the process. A complete and accurate history of the patient needs to be collected [
In cases where more than one year has passed a new evaluation is necessary because the new deposition of GAGs may have altered the previous airway anatomy, the cardiac and pulmonary functions, causing impairments such as Obstructive Sleep Apnoea Syndrome (OSAS).
Accurate OE includes airway inspection, neurologic, cardiac, ear, nose, and throat (ENT), and visceral assessment.
Laboratory: complete blood count (CBC), arterial blood gas analysis (ABG analysis), serum electrolyte, and liver enzymes. Pulmonary function test: vital capacity, functional residual capacity, and total lung capacity (often reduced for skeletal restriction). Tracheobronchoscopy and laryngoscopy [ ECG, echocardiography, angiography, cardiac stress test to evaluate valvular structure and functioning, ventricular dimension, and kinetics [
The previous study of the airway morphology by imaging is fundamental (Rx, computed tomography (CT), and magnetic resonance imaging (MRI)). Chest X-ray: pneumonias and atelectasis, often without symptoms, requiring antibiotics and respiratory therapy. Cervical spine X-ray (laterolateral): to identify an incomplete anterior ossification of the atlas, a dens dysplasia, and possible dislocations (especially in Morquio and Hurler syndromes). Multidetector computerized tomography (MDCT) images [
Kadic and Driessen [ Cervical spine X-ray (flexion): to demonstrate possible tracheal collapse in Morquio syndrome children, a contraindicating condition to head hyperextension during endotracheal intubation. Polysomnography: gold-standard investigation for OSAS evaluation [ Somatosensory evoked potentials: to detect early cord compression [ Measurement of CSF pressure if communicating hydrocephalus is suspected [
Premedication, especially with opioids, enhances the risk of respiratory depression, but is often necessary and used for a better preoperative management of uncooperative children. Furthermore, a certain drug resistance is possible. So particular attention to patients with severe respiratory failure is advisable [
Antibiotic prophylaxis is a topic of debate; however, in the most recent studies, there is a trend towards avoiding it because it is unnecessary [
Anesthesia should be administered only by an experienced anesthesiologist, who has performed the procedure in the past on this kind of patient, supported by a trained team in emergency situations requiring tracheotomy.
The choice of the anesthetic technique is another point of interest: general anesthesia is dangerous in MPS subjects, and, when possible, local anesthesia with peripheral blocks should be preferred [
The choice of technique depends on the anesthesiologist’s skill to maintain spontaneous breathing until intubation. Intravenous induction is possible (thiopentone, propofol, midazolam, ketamine) as well as inhalation induction (halothane or sevoflurane) or fiberscope intubation in an awake patient (topical anesthesia) slightly sedated. An important advantage of the fiberscope is the possibility of intubation otherwise impossible, maintaining spontaneous breathing. However, great skill is required especially because of the difficulty to use the nose-tracheal approach (i.e., bleeding). It is also essential to use a small fiberscope diameter (patient size and airway infiltrations).
Inhalation induction and spontaneous breathing maintenance or intravenous induction with fast acquisition of airway control gave positive results in general anesthesia [
Airway abnormalities are a consequence of morphological differences, which often occur in many forms of MPS and imply a predisposition to obstruction and difficult intubation (incidence 25%, failed 8% in Santos et al. [
Moreover, during general anesthesia, there is a loss of the muscle tone as a result of decreased cortical influences, chemoreceptor drive, and mechanoreceptor input. There is also a direct inhibition of the airway muscle tone, of the neural activity reflex and of the protective arousal responses. The favorite site of collapse is the velopharynx [
Spontaneous breathing is absolutely essential until the achievement of a successful intubation or (at least) until the clear demonstration of the possibility of mask ventilation [
Tracheal intubation should be accomplished during deep inhalation anesthesia without the use of neuromuscular blocking drugs, because the loss of muscle tone may cause the prolapse of the soft supraglottis tissues, acting as a ball valve [
Since intubation is difficult in 50% of cases, blind intubation is advisable; alternatively, it is possible to use a fiber optic flexible bronchoscope [
In 1996, Moores et al. [
Walker et al. [
The largest series of data is available from Mahoney et al. [
Direct laryngoscopy evidenced in 5 out of 19 patients macroglossia, oropharyngeal and supraglottis redundant tissue, thickened epiglottis, and reduced tracheal and bronchial diameter. All 19 patients underwent adenotonsillectomy: 5 (26%) required CPAP before surgery, 3 (11%) urgent tracheotomy [
Concordant results, especially regarding obstruction of the airway, can be found in other retrospective studies.
When it is not possible to exclude odontoid dysplasia (IH, II, IHS, IV, VI, and VII), keep a neutral position of the head through cervical collars, premoulded plaster devices [
Osthaus et al. [
Laryngeal mask airway (LMA) allows a good airway control without tracheal intubation. This device is used by some authors in MPS patients [
Despite this, there is a high incidence of failure in guaranteeing airway patency through such a device. Busoni and Fognani published a case report to show how LMA caused inspiratory stridency and airway obstruction in an MPS patient (Hunter syndrome) which were solved by mask removal [
Another option is represented by supraglottis devices (I-gel) that allow ventilation and oxygenation during endotracheal intubation attempts [
In some cases, direct laryngoscopy was used in children as described by Suh et al. in a case report published in 2010, concerning a 9-month-old boy affected by Maroteaux-Lamy syndrome [
The progression of the disease implies a more difficult management in adult patients, with special concerns about the airways, as witnessed in two case reports. Ingrosso et al. [
Nicolson et al. [
A proper humidification and heating of the inspiratory mixture is essential, and it is important to avoid hypovolemia to keep tracheobronchial secretions fluid [
Complications of awakening after anesthesia are apnea, bronchospasm, cyanosis, and respiratory failure [
Early extubation, immediately after the procedure, reduces the risk of urgent tracheotomy [
Furthermore, regardless of the positive result of surgery, other complications are laryngeal or subglottic edema [
Certain patients may require reintubation or urgent tracheotomy, because of their incapability to maintain patency after extubation [
Postoperative edema is possible until 27 hours after anesthesia [
Walker et al. [
Other possible complications are postoperative hypoglycemia [
Postoperative treatment includes steroid prophylaxis to reduce edema, standard treatment for patients with upper airway obstruction (biPAP, CPAP [
MPS children are high anesthetic risk patients because of airway narrowing, bone dystrophy, cardiac illness, and neurological impairment. They require the cooperation of counselors with different professional competences such as otorhinolaryngologists (ORLs), anesthesiologists, and surgeons, under the coordination of a single person—the counselor caring for the child—who keeps the situation for the single patient under control. The best management we can obtain is with the creation of a communicative multidisciplinary team, available to cooperate with other professionals worldwide. The administration of anesthesia should be performed only in specialized centers by experienced anesthesiologists and trained personnel. Indication for surgery should be carried out only after consulting the anesthesiologist, who has the duty to discuss risks and benefits with the parents.
All of this is maimed at improving the quality of life of both patients and families, as can be seen through the use of surveys [