The high anesthetic risk for MPS patients consists primarily in the predicted difficult airway and in the presence of comorbidity. This underlines the critical role of an appropriate anesthesiological plan.
Pre-operative evaluation
A thorough preoperative evaluation must be carried out using a multidisciplinary approach. The anesthesiologist must examine all the diagnostic tests performed. Ear, nose, and throat (ENT) assessment and the Mallampati classification system (based on the visibility of tonsils, pillars, uvula, and soft palate) can evaluate nostril narrowing, adeno-tonsillar hypertrophy and macroglossia, nasopharyngeal obstruction, and supraglottic narrowing [31]. Whenever surgery is planned, it would be desirable to perform a computed tomography scan (CT) of the airway with an extension of the scan to create a three-dimensional reconstructions of the trachea [32]. Sleep studies conducted overnight during natural sleep can detect obstructive sleep apnea and could suggest the need for postoperative monitoring and therapies in the intensive care unit to maximize respiratory function [8, 13, 14, 31, 33]. Patients may develop airway occlusion upon neck flexion and adopt a “sniff position” to preserve airway patency [31]. Compromised respiratory function due to restrictive disease with decreased lung volumes and ventilation-perfusion mismatching is a possible complication. Chronic hypoxemia over time can have cardiovascular consequences, such as pulmonary hypertension leading to cardiorespiratory failure [8, 13, 14, 19]. The results of pulmonary function tests must be taken into consideration [14, 31, 33]. Examinations or functional assessments and routine spine x-rays, MRI, and flexion-extension cervical film assessments may confirm the potential for atlanto-axial subluxation, which is a contraindication for cervical extension during endotracheal intubation. Early signs of myelopathy could eventually be an indication for prophylactic cervical spine fusion. Intraoperative neuromonitoring with somatosensory evoked potentials is suggested during surgery to detect any acute spinal compression [1, 14, 21, 25, 28, 30, 34,35,36]. A complete routine cardiac evaluation (electrocardiography, blood pressure reading, and echocardiography) is mandatory before surgery. The assessment of current hemodynamic stability can give further indications for the need for additional medications or tests [37,38,39]. Cardiac manifestations may be severe valvular disease (valve thickening and dysfunction dysplasia of the subvalvular apparatus), unstable coronary syndromes, cardiomyopathy, pulmonary hypertension, decompensated heart failure, and significant arrhythmias. Moreover, atrial dilatation, endocarditis, myocarditis, and ventricular aneurysms might be observed [14, 19, 20, 29, 37,38,39,40].
Premedication
Narcotic premedications are to be avoided if airway problems are anticipated, as is usually the case [3, 33]. If a benzodiazepine is administered as premedication, patients should be strictly monitored with a pulse oximeter [1, 40]. The use of available oral drying agents is helpful [40]. Perioperative treatments may include nasal decongestants to control excessive mucus production and steroids to reduce swelling [10, 14, 22, 31].
Induction of anesthesia
The first consideration is to identify the correct positioning of the patient. Useful information includes a history of obstructive sleep apnea and the child’s favorite sleeping position since this may be the position in which the airway is held open [7]. A small shoulder roll improves airway patency during mask ventilation [5, 27]. Placing the child in a lateral position can avoid airway obstruction by the tongue. Almost all the intravenous and inhaled anesthetics have been described in the studies that are included in the bibliography. Inhalational induction with sevoflurane is sometimes unavoidable to establish reliable venous access. Two-person mask ventilation is often necessary. The use of an upside-down facial mask has been described [3, 33]. The skill lies in being able to keep the airways open and secure them. Ketamine should be the ideal drug [13], but it may increase the amount of secretions. Full apneic doses of narcotics should not be administered before tracheal intubation [33] and it is not advisable to paralyze MPS children before securing the airway [34]. Spontaneous ventilation techniques using oxygen and a high-concentration volatile anesthetic is commonly used. Insertion of an LMA will often improve ventilation [7, 32, 41,42,43,44,45].
Endotracheal intubation
MPS patients may be very difficult to intubate, regardless of the choice of equipment [27]. The use of videolaryngoscope alone or in combination with FOB has proved to be a useful tool for intubating the trachea [3, 8, 11, 17, 18, 27, 42, 43]. If FOB is not available, displacing the tongue anteriorly by manual retraction helps to access the larynx once the videolaryngoscope blade is inserted. Difficulty with nasal FOB is to be expected because of the narrow nasopharyngeal path and GAG infiltration of the adenoids [4, 9, 20]. Intubation can also be obtained by passing the fiberscope through the LMA [11, 43, 44], and the new supraglottic airway device makes this procedure even easier [46, 47]. The equipment is shown in Fig. 2. The correct size of the endotracheal tube is often smaller than that predicted for the patient’s age to reduce the risk of postoperative subglottic edema [9]. When the patient has a significant risk due to spinal cord compromise from an unstable cervical spine, it is advisable to monitor the somatosensory evoked potentials throughout the perioperative period to assess spinal cord integrity during intubation and positioning maneuvers. Even though manual in-line stabilization of the neck might be sufficient to protect the spinal cord from excessive movements during intubation, there is the risk of increasing the index of difficult intubation [20, 21, 23].
Once general anesthesia is started, the trachea and bronchi can be monitored with a FOB, and a plan for extubation can be made.
Extubation
Extubation of the trachea at the end of general anesthesia may represent another major risk. A postobstructive pulmonary edema may further worsen the airway patency, resulting in the need for urgent reintubation or tracheostomy [1, 9, 16, 48]. Patients should be extubated when fully awake and after having performed a leak test, and then monitored closely for early signs of upper airway obstruction. However, if at the end of surgery extubation criteria are not present, awakening may be delayed and carried out in the intensive care unit to allow the safe weaning from mechanical ventilation, aggressive chest physiotherapy, and the early detection and treatment of respiratory infectious complications [3, 12, 16, 20, 21, 40]. Preoperative determination of the child’s favorite sleeping position may give some information as to the most appropriate positioning to use as the residual effects of the general anesthetic dissipate [34].
Tracheostomy
Tracheostomy can be indicated to treat refractory progressive upper airway obstruction or for emergency airway management but, in these patients, placement of the tracheostomy tube can be difficult due to the distortion and to the laxity of the trachea. Tracheostomy may be further associated with stomal narrowing, granulation formation, infrastomal tracheal stenosis, wound infection, and tracheomalacia. For these reasons, the prophylactic use in cases of elective surgery is not routinely recommended, especially in children, and should be discussed in depth with the multidisciplinary team [9, 49,50,51].
Anesthesia versus sedation
Radiological evaluations and other tests may require deep sedation in younger or uncooperative patients. Performing deep sedation in remote locations can be a challenge due to the risk of airway obstruction and desaturation. The decision to use deep sedation must be made based on the respiratory conditions of the individual patient; some of them are eligible for deep sedation with native airways [5] while, for others, LMA in spontaneous ventilation or general anesthesia with endotracheal intubation is preferable [12, 52].
Regional anesthesia
The use of regional or blended anesthesia in MPS patients is still a controversial topic; a careful evaluation of the risk–benefit ratio has yet to be performed. The limited literature consists of case reports of single patients or of small groups of patients. Some successful cases reports are described [34, 53], sometimes associated with deep sedation [54]. Theroux et al., in a retrospective study on MPS IVA children, describe six cases of successful epidural catheters placed for postoperative analgesia. A caudal approach was preferred to a lumbar one in four children because of irregularities of the vertebral bodies and frequent kyphosis [27]. On the other hand, a case of failure is also reported, where the authors hypothesize the deposit of mucopolysaccharides in either the general epidural space or in the sheath of the nerve fibers which prevented the direct access of the local anesthetic to the nerve [55]. Furthermore, Drummond et al. report a case of complete paraplegia in a girl with MPS IV immediately postoperatively after an apparently uneventful lumbar epidural-general anesthesia; the patient sustained a spinal cord infarction, likely due to spinal cord compression or to hypoperfusion. The epidural anesthetic contributed to the delay in the recognition of the paraplegia. The authors concluded that it may be prudent to avoid the use of epidural anesthesia, to support blood pressure in the presence of even moderate spinal stenosis, and to avoid flexion or extension in intraoperative positioning [56].
Adult patients
With improved care, the life expectancy of patients with MPS continues to increase. They often need surgical intervention for a variety of indications. Thus far, very little literature is available about adult patients, but the increased life expectancy associated with enzyme replacement therapy and hematopoietic stem cell transplantation goes along with an increased demand for surgery and anesthesia. Aging can be associated with severe narrowing of the larynx or trachea and with severe obstructive sleep apnea [26]. The progressive involvement of many organs leads to death. Several cases are reported of successful intubation [36, 46, 50, 57,58,59,60,61] and, in most cases, FOB was used. In one case, a pre-recovery tracheostomy was performed to avoid extubation problems [51]. Cade et al. described a case of MPS VI in which both the supraglottic and subglottic tissues were notably enlarged, and the upper trachea was abnormal. Despite significant facial swelling at the end of the operation, the trachea was extubated without incident [61]. Two papers describe three cases where adults with MPS IVA died of acute respiratory distress syndrome due to systemic storage materials in multiple tissues [62] or to distortion and laxity of the bronchial tree [51].
The effect of therapy on airway management
Although early diagnosis and therapy give promising results, there is not enough conclusive evidence of the effectiveness of therapies in reducing anesthesiological risks. Two retrospective chart reviews published in 2012 show that enzyme replacement therapy alone does not reduce the incidence of difficult airway management in MPS I, II, or VI, while hematopoietic stem cell transplantation patients have a much lower incidence of airway complications [12, 63]. Another retrospective study reports that enzyme replacement therapy followed by hematopoietic stem cell transplantation does not decrease the overall incidence of difficult airway management related to general anesthesia [42]. A recent prospective study on MPS IVA children who underwent hematopoietic stem cell transplantation shows fewer surgical interventions than for untreated patients, while surgical frequency for patients treated with enzyme replacement therapy was not lower than that of untreated patients [64]. On the other hand, many lines of evidence support the opinion that the treatment of patients with MPS should occur early, at least at the onset of clinical disease, if not presymptomatically [65].