Anesthesia for patients with mucopolysaccharidoses: Comprehensive review of the literature with emphasis on airway management

Abstract

Mucopolysaccharidoses (MPS) are rare, inherited, lysosomal storage diseases that cause accumulation of glycosaminoglycans, resulting in anatomic abnormalities and organ dysfunction that can increase the risk of anesthesia complications. We conducted a systematic review of the literature in order to describe the anesthetic management and perioperative outcomes in patients with MPS. We reviewed English-language literature search using an OVID-based search strategy of the following databases: 1) PubMed (1946-present), 2) Medline (1946-present), 3) EMBASE (1946-present), and 4) Web of Science (1946-present), using the following search terms: Mucopolysaccharidosis, Hurler, Scheie, Sanfilippo, Morquio, Maroteaux, anesthesia, perioperative, intubation, respiratory insufficiency, and airway. The review of the literature revealed nine case series and 27 case reports. A substantial number of patients have facial and oral abnormalities posing various challenges for airway management, however, evolving new technologies that include videolaryngoscopy appears to substantially facilitate airway management in these patients. The only type of MPS that appears to have less difficulty with airway management are MPS III patients, as the primary site of glycosaminoglycan deposition is in the central nervous system. All other MPS types have facial and oral characteristics that increase the risk of airway management. To mitigate these risks, anesthesia should be conducted by experienced anesthesiologists with expertise in using of advanced airway intubating devices.

INTRODUCTION

Mucopolysaccharidoses (MPS) are rare, inherited, lysosomal storage diseases characterized by deficiencies in 11 different lysosomal enzymes involved in the metabolism of glycosaminoglycans, previously known as mucopolysaccharides. These enzyme deficiencies result in progressive, widespread accumulation of partially degraded glycosaminoglycans in the lysosomes of various tissues and organs; the characteristic patterns of accumulation form the basis of MPS classification into seven types of progressive MPS diseases (Table 1) [1-5]. With the exception of MPS II which is inherited as an X-linked recessive disorder, all other MPS disorders are inherited in an autosomal recessive pattern; therefore, affecting males and females equally [1]. MPS can be grouped into four broad categories according to their dominant clinical features: 1) MPS I, II, and VII affect soft tissue storage and the skeleton with or without brain disease; 2) MPS VI affects both soft tissues and the skeleton; 3) MPS IVA, IVB are primarily associated with skeletal disorders; and 4) MPS III A-D primarily with central nervous system disorders. Table 1 summarizes enzymatic defects, prevalence, and clinical presentation of various MPS types. The published prevalence estimates vary widely between different studies (http://emedicine.medscape.com/article/1115193-overviewaccessed May 29, 2017). Depending on MPS type, glycosaminoglycan accumulations can occur in various organs resulting in cardiovascular, pulmonary, gastrointestinal, neurologic, and musculoskeletal dysfunction [1]. Glycosaminoglycan accumulation in the upper airway results in hypertrophy of adenoids, tonsils, tongue, and laryngopharynx, which may all pose difficulty for anesthetic airway management. This is especially important because MPS patients frequently require surgical interventions with anesthesia. For example, one MPS I registry showed that 75% of patients underwent at least one procedure requiring anesthesia [6]. The Hunter Outcome Survey that included 527 patients with MPS II reported that 83.7% of patients required a surgical intervention at some point [7].

TABLE 1.

Genotype, phenotype, and clinical manifestations of patients with MPS

Because altered anatomy of the airway and facial structures can complicate airway management [2-5], both mask ventilation and endotracheal intubation, the primary aim of the present study was to perform a comprehensive systematic review of the literature and summarize the published experience of airway management in patients with MPS.

MATERIALS AND Methods

We reviewed the literature for reports of perioperative course and airway-related anesthetic complications in patients with MPS. We conducted an English language literature search using an OVID-based search strategy of the following databases: 1) PubMed (1946-present), 2) Medline (1946-present), 3) EMBASE (1946-present), and 4) Web of Science (1946-present). We used the following search terms: Mucopolysaccharidosis, Hurler, Scheie, Sanfilippo, Morquio, Maroteaux, anesthesia, perioperative, intubation, respiratory insufficiency, and airway. Reference lists of identified reports were searched for additional relevant publications.

RESULTS

The systematic review of the literature identified nine case series, and their airway management is summarized in Table 2 [5,8-15]. In addition, we identified 27 individual case reports and these patients’ characteristics and their airway management is summarized in Tables 3 and 4 [7-10,16-38]. Figure 1 is a pie chart that summarizes airway management in a case series of MPS patients who underwent anesthesia at Mayo Clinic between years 2000 and 2015, which was reported in the Canadian Journal of Anaesthesia [15]. In that report, we described 18 MPS patients who underwent 49 procedures (there were 2, 1, 4, 7, and 4 patients with MPS Type I, II, III, IV, and VI, respectively) [15]. Finally, there is an isolated description of a 5-year-old boy with MPS II who underwent an inguinal hernia repair under a spinal anesthetic out of concern that the airway management would be difficult [39].

TABLE 2.

Outcomes of airway management in various MPS phenotypes from case series

TABLE 3.

Airway characteristics in patients with MPS I and II with details of airway management from individual case reports

TABLE 4.

Airway characteristics in patients with MPS IV and MPS of unknown type with details of airway management from individual case reports

FIGURE 1.

Anesthetic airway management in a series of 49 Mayo Clinic patients with various types of mucopolysaccharoidoses.

DISCUSSION

Patients with MPS have multiple comorbidities, many of which require surgical interventions. Because MPS is associated with specific phenotypic facial and airway characteristics, substantial challenges for perioperative airway management may be expected. Such challenges were confirmed in our recently reported MPS case series [15], as well as in earlier reports [3,5,8,9]. In addition, failed tracheal intubations requiring emergency tracheostomy have also been reported [3,5,8].

In two case series difficulty with mask ventilation has ranged to 7% and 14% of MPS patients [8,9]. Furthermore, our literature review suggests that mask ventilation is less likely encountered in MPS III patients. Kamata et al. [13] reported no difficulties in mask ventilation in a cohort of MPS III patients, albeit mild upper airway obstruction was noted during 14 procedures (33%), which was resolved with simple head/jaw maneuvering/positioning. Another review of a large MPS III series reported no problems with mask ventilation in 86 anesthetics [12]. All nine MPS III patients in our recent series from Mayo Clinic had uneventful mask ventilation during anesthetic induction [15].

The overall incidence of difficult tracheal intubation, in case series of various types of MPS, ranges between 28% and 44% [5,8,9]. Management of endotracheal intubations in MPS III patients appears to be less difficult. Specifically, Cingi et al. [14] reported 25 children with MPS III who underwent 73 anesthetic with no case of difficult intubation, and all intubations views were graded as Cormack-Lehane 1-2. This may not be surprising because MPS III is associated mostly with central nervous system disorders and less with glycosaminoglycan accumulation in oral soft tissues. Mayo Clinic experience with MPS patients since year 2000 includes 18 MPS patients who underwent 49 procedures (Figure 1) [15]. In seven instances, the patients presented for surgical procedures were already tracheally intubated or presented with tracheostomy (all were MPS IV and VI). Six anesthetics were conducted with mask ventilation as a primary airway management, and ventilation was difficult in two patients on two occasions (both were Type IV MPS [Morquio syndrome]). In 15 procedures, tracheal intubation was electively secured with either fiberoptic intubation or videolaryngoscope (VLG), and VLG was used as a rescue technique in two additional patients who failed the initial planned approach. In 19/36 (53%) procedures, airway management was successful with primary planned approach: direct laryngoscopy or laryngeal mask supraglottic airway. In our series of patients, there were nine patients with MPS III, and while all were “easy masks” one was describe as “difficult direct laryngoscopy”, suggesting that even i

n this MPS group caution should be exercised when managing the airway. Facial characteristics of one our patient with MPS VI (known as Maroteaux-Lamy syndrome) was deceiving, as it did not predict difficult mask ventilation (Figure 2). This 15-year-old female had obstructive sleep apnea, maxillary hypoplasia, high-arched palate, macroglossia, narrow hypopharynx, and compromise of the cervical spinal cord at the foramen magnum. Mask ventilation required two hands and a jaw thrust. Three attempts to place a laryngeal mask airway failed. Endotracheal intubation was successful with a VLG, albeit aided by a fiberoptic bronchoscope. The fiberoptic bronchoscope was used by a second anesthesia provider to locate the glottic opening, as VLG provided only a view of the epiglottis. After inserting the fiberoptic bronchoscope through the glottis opening, our endotracheal tube was guided over the scope into the trachea. In our report, 16.7% (3/18) patients had a true difficult airway (failed primary technique) [15]. This percentage likely represents an underestimate of difficult airway in MPS patients because anesthesiologists electively used a fiberoptic bronchoscope or VLG in 15 out of 36 procedures, suggesting a concern for potential difficult intubation. VLG-assisted intubations have been introduced only recently as an alternative intubation method, and in our series of MPS patients we found that since its introduction in 2009, the majority of cases were intubated using VLG, and all attempts were successful [15]. Theroux et al. [40] retrospectively examined intubations of 28 MPS patients undergoing 108 anesthetics and similarly observed that VLG became a preferred method for tracheal intubation for MPS patients. Megens et al. [9] reviewed the success rate of tracheal intubation using different tools: direct laryngoscopy was difficult in 16 out of 55 anesthetics, VLG was successful in 8 out of 9 anesthetics, and fiberoptic intubations were performed without difficulty in only 2 out of 10 cases. With the more widespread availability of VLG, this technique may become a preferred technique for endotracheal intubation in patients with MPS.

FIGURE 2.

(A and B) A 15-year-old girl with mucopolysaccharidosis Type VI. Despite the fact that her facial characteristics gave impression that her airway is “manageable,” she had difficult mask ventilation, and 3 failed attempts to place a laryngeal mask airway. Placement of endotracheal tube was successful with a video laryngoscope aided by fiberoptic bronchoscope (see discussion for details). Published with the consent of patient’s legal representative.

Besides various airway issues, patients with MPS have other comorbidities that may have an impact on ventilation. Specifically, they frequently have restrictive or obstructive lung disease, recurrent lung infections, and obstructive sleep apnea [5]. Propensities for bronchospasm and oxyhemoglobin desaturation may complicate airway management in MPS patients. Furthermore, skeletal dysplasia such as atlantoaxial instability, spinal cord compression, limited neck mobility, pectus carinatum, and scoliosis is common [16]. Finally, there may be a high degree of tracheal narrowing in patients with MPS IV A (Morquio A). Evaluation of 28 MPS IV A patients with sagittal magnetic resonance imaging (MRI) scans found 68% had at least 25% tracheal narrowing and 29% had >75% narrowing due to a combination of a narrow thoracic inlet, tracheal growth, and tortuous brachiocephalic artery [41].

CONCLUSION

Patients with MPS have multiple comorbidities requiring frequent surgical procedures with anesthesia. With an exception of MPS III, all other MPS types have facial and airway characteristics which may create a challenge for anesthetic airway management. To mitigate the risks of airway mismanagement in patients with MPS, anesthetic planning should include experienced anesthesiologists and expertise in using a full array of advanced airway devices.

DECLARATION OF INTERESTS

The authors declare no conflict of interests.