Strategies to manage critical clinical situations in adults with MPS
Alongside collection of cases, healthcare professionals (HCPs) also provided key strategies that support the management of patients with MPS through critical clinical situations. These are summarised in Table 1.
The preoperative assessment
The importance of a thorough preoperative assessment was highlighted as being key in bringing together the members of the MDT who will be involved in managing the critical clinical situation, ensuring that all necessary information is obtained and an expert opinion is provided (Supplementary information: Multidisciplinary review and MPS Passport). The multidisciplinary review allows input from multiple disciplines, including metabolic specialists, cardiologists, anaesthetists, ear, nose and throat (ENT) surgeons, respiratory specialists, radiologists, neurologists and physiotherapists (Figure). The outputs from this review are compiled into an MPS Passport, consisting of a clinical letter, images and videos, allowing any clinicians involved in the future management of a critical clinical situation, or clinicians located at different sites, to gain a thorough understanding of individualised recommendations and any associated challenges. This MPS Passport was developed by the Department of Anaesthetics at the Salford Royal NHS Foundation Trust, Salford, UK, and provides a reproducible, reliable approach for each patient. The multidisciplinary review is held as a single appointment, which is convenient for the patient and their carers, and also allows viewpoints from different specialities to be considered together. The images and videos can also be used to help patients and carers to understand the risks associated with any abnormalities of their airways or other investigation results.
As the standard tools and assessments used by anaesthetists may not be adequate for the assessment of patients with complex airways, such as those with MPS, a more thorough assessment involving an ENT consultant should also be carried out preoperatively (Supplementary information: Assessing the airways and preparing for emergency tracheostomy). Assessing cardiac risk may be challenging because of reduced mobility and chest deformities, which mean that tests that are used routinely in the general population, such as echocardiograms (ECHO) under stress, are not always suitable for patients with MPSs. Other suitable testing strategies may include transthoracic or transoesophageal ECHO, electrocardiogram (ECG), carotid intimal media thickness measurement and computed tomography (CT) coronary angiogram, although a short neck or inability to lie in the supine position due to bone deformities and lack of cooperation may make these studies less feasible for some MPS patients. In high-risk patients, and those expected to undergo long surgeries, intra-arterial blood pressure monitoring may be required.
Neurological symptoms in MPS disorders, such as epilepsy, impaired cognition and behavioural symptoms, are associated with accumulation of the GAG heparan sulphate, and these symptoms may become apparent or worsen as the MPS disorders progress and patients reach adulthood (9, 26-28). The seizure threshold may be affected by anaesthetic agents and is managed by continuous intravenous AEDs administration during surgical procedures (29). Aside from being used to treat epilepsy, antiepileptic drugs (AEDs) may also be used to manage behavioural symptoms, such as aggression and low mood (30), and plans will need to be made to ensure appropriate medication can continue during recovery. Electrolyte imbalances should be corrected in patients’ blood prior to and monitored after the surgery, as electrolyte disturbances are common causes of confusion in the hospital setting (31).
Patients undergoing transition to adult care from a paediatric setting
The complex surgical procedures in MPS disorders require clinical expertise that can be limited in the adult care setting (23). Therefore, if an adult patient has not yet completed transition, and is still under some level of paediatric care, the MDT can assess if it would be most appropriate for the patient to remain in the paediatric setting during the perioperative and recovery periods, and for the surgery to be conducted by a paediatric team. If a patient develops an acute illness during the transition period, the MDT often decides that it is in the best interest of the patient to stay under the paediatric service while the critical clinical situation is resolved.
Engagement with the patient and family
The MDT must also prepare the family for any potential complications and negative surgical outcomes, such as an unsuccessful procedure and the risk of death during or after the procedure (Supplementary information: Discussing procedures with the patient and family).
Supporting the multidisciplinary team
Key members of the MDT and considerations for constituting the MDT are shown in the Figure and Table 1 respectively. HCPs with specialist knowledge and experience in paediatric MPS can provide guidance on or even undertake specific tasks. Furthermore, expertise may also be sought from external centres, and indeed HCPs may travel to provide practical support during procedures, or virtual MDTs may be established to allow input from multiple external experts. Although virtual MDTs do provide opportunities for geographically distant experts to be involved, this must be balanced with these experts having a less in-depth historical knowledge of the patient and their pre-surgical assessment results. Patients may also be referred to an expert in a distant centre, but this may delay decision-making and can cause distress if patients need to travel long distances or be assessed by unfamiliar HCPs. However the MDT is structured and supported, it should be ensured that specialists with experience of MPS either perform or provide guidance on the procedure (32, 33).
Specialised surgical equipment and surgical preparations
A full review of equipment and assessment results by the surgical team and an MPS expert prior to surgery will ensure that all requirements are in place (Supplementary information: Surgical preparations). Access to intraoperative monitoring options should also be investigated before surgery is performed. To avoid spinal injury, sensory injury with dysesthetic pain, and/or loss of proprioception, it is critical to maintain a neutral neck position during all surgeries, including during intubation and extubation (33). Motor evoked potential and somatosensory evoked potential measurements may both be used to assess the risk of ischaemia and paraplegia, and are key in managing surgical risk in MPS patients with complex spinal abnormalities (34), although these options may only be available in specialised spinal and neurosurgical units. The requirement to access this equipment, and the need to work alongside experts able to interpret and promptly respond to the results, reinforces the need to carry out surgery in MPS in expert centres with specialist teams either carrying out or providing close guidance on the procedure (32, 33).
Patients with cochlear implants should not undergo procedures involving diathermy in the head and neck regions, although surgeons may not always be aware of this (35), and it is key that all members of the surgical team should be informed of any factors that would require a divergence from standard surgical procedures.
A very small number of patients may also have implanted intrathecal devices to deliver baclofen to treat spasticity and dystonia, although these have not been shown to be effective in all MPS. The clinical experience of baclofen use in MPS patients is limited to few cases and the benefits were variable (36-38). Complications associated with baclofen pumps are a frequent occurrence, and repeated surgeries are often required to manage these complications (36), which typically involve infections or mechanical failures.
The recovery of the patient is also a complex, multidisciplinary process, which needs to be responsive to the outcome of surgery and any emergency procedures that were needed. Due to intubation during surgery and the accompanying soft tissue manipulation, patients may also be at risk of oedema of the airways. As this is frequently coupled with other respiratory features of MPS, post-surgical observation in an intensive care unit is a key stage of the initial recovery period (32, 33), and a place in such a unit should be available for all MPS patients in the 24 hours following surgery. Feeding plans need to adapt as the patient recovers, and individualised physiotherapy requirements should be in place to support the patient’s rehabilitation (Supplementary information: Post-surgical care).
For the first 4 weeks post-surgery, it is recommended that ERT infusions are not provided, which is due to several key factors. First, the risk of anaphylactic reactions to ERT during sepsis or fever is higher; recommendations for MPS IVA, and safety information for ERT for MPS I state that infusions should be avoided in this acute post-surgical setting as patients may experience sepsis or fever during recovery (32, 39). Second, adverse events associated with ERT can include fever and chills (14, 32, 33), and if ERT were provided soon after surgery, determining the cause of such symptoms as ERT-related or surgery-related would be challenging, leading to difficulties in managing the symptom. Third, staff in the post-surgery intensive care or recovery setting may not be familiar with administering ERT infusions and the precautionary procedures that should be carried out.
Continuation of ERT during longer periods of hospitalisation is likely to be affected by centre-specific and national circumstances. For example, in the UK, ERT is subject to additional costs for inpatients. In Germany, patients can continue ERT as outpatients, but coverage for inpatient ERT costs need to be negotiated with insurance companies. In contrast, patients in Russia can continue their infusions as inpatients. In Spain, there are no cost implications for continuing ERT for inpatients, although, in some regions, decisions to maintain or stop ERT would be taken by a specialist lysosomal disorders treatment committee. Due to this variation, an understanding of any restrictions is vital, and plans for infusions during the recovery period need to form a key part of the post-surgery strategy.
Post-surgical cognitive function
Aside from the physical aspects of a patient’s health status, the MDT must also consider the mental health and cognitive abilities of the patient. Several MPS disorders are associated with cognitive deficits, behavioural issues and epilepsy that need to be considered when assessing the patient’s recovery or their ability to communicate that they are in pain (4, 40). Postoperative delirium is associated with a poor prognosis, and has been associated with baseline cognitive function, and cardiac and emergency surgeries, so it should be kept in mind when monitoring adult MPS patients post-surgery (41). Postoperative cognition may also be affected by the use of some sedatives (42), analgesia in some populations (43), dehydration (44), preoperative infection (45), and some AEDs (46). In MPS additional care should be taken to ensure that the patient is appropriately assessed, and that post-operative cognitive changes do not impact further on any pre-existing neurocognitive deficits. Plans to continue AEDs need to be in place, potentially with input from a neurologist, if the patient’s usual medication would interact with other perioperative drugs or a different method of AED administration is needed (29).
Critical clinical cases and their specific challenges are summarised in Table 2. These cases illustrate examples of the types of challenges that might be encountered during critical clinical situations in patients with MPS but should not be considered exhaustive. Challenges associated with these surgical cases and critical clinical situations, and resolutions to these challenges, are shown in Table 3 and Table 4, respectively.