Despite significant progress in the search for disease modifying agents, the chronic, progressive nature of Friedreich ataxia (FRDA) continues to have a profound impact on the health and well-being of affected individuals. As for those living with other rare diseases, individuals with FRDA often find it difficult to access expert specialist multi-disciplinary care for long-term, evidence-based management. In response to this need, the Consensus Clinical Management Guidelines for Friedreich Ataxia were developed and published in 2014. Since this time, some new evidence in managing FRDA has emerged warranting an update of the Clinical Management Guidelines (CMGs), but the challenges of developing guidelines for rare diseases remain. In particular, the lack of adequately powered studies means that many management recommendations are based on low-certainty evidence. Deciding to update the guidelines provided an opportunity to consider alternative methods of grading the evidence and establishing the strength of the recommendations, to help overcome some of these challenges.

In 2019, the RARE-Bestpractices Working Group published a framework for developing guidelines in rare diseases using the robust Grading of Recommendations Assessment and Evaluation (GRADE) system2, which was adopted for this iteration of the Friedreich ataxia CMGs. In this approach, the GRADE system is supplemented with three strategies specific to rare diseases: a) reviewing and including literature in like conditions, thus providing “Indirect evidence”, b) the systematic collection of expert clinical observations and/or patient perceptions via bespoke “structured observation forms” and, c) the use of available clinical registry data. Moreover, the GRADE framework ensures a transparent and dynamic process of continual updating of the recommendations as new evidence emerges.


In 2020, an executive guidelines panel comprising seven international clinicians was commissioned to provide oversight of the guidelines development process and endorse the final recommendations. The guidelines panel invited international expert clinicians and researchers (the authors) to write background chapter content and develop recommendations for topics that were assigned according to their particular expertise. Individuals with FRDA and/or their families were included throughout the development of the guidelines to provide a lived perspective of FRDA, specifically contributing to the development of the topics and the lay summaries of the clinical recommendations.

Using the GRADE methodology, the authors developed clinical questions pertinent to their particular topics in the Patient, Intervention, Comparison, Outcome (PICO) format, which guided the literature search (from 2014 to June 2020). The search was completed by two methodological experts who then summarized and synthesized the evidence using the GRADE structure. Evidence profiles, natural history registry data, expert clinical observations and feedback from individuals living with FRDA were used by the authors in a structured, transparent process (using evidence to recommendation tables) to develop the final clinical recommendations.

Based on the evidence and other information, the authors graded the strength of the recommendation and the level of evidence for each recommendation. For the rating of the strength of the recommendation, in addition to evidence from studies in FRDA, evidence from like conditions, clinical experience and expert consensus was taken into account when published evidence was not available. The level of evidence was based on published evidence from studies in FRDA. If there was no published evidence in FRDA, evidence from other like conditions or clinical expertise may have been used to make the recommendation – this was graded as ‘very low’ or in some cases ‘low’ level evidence. See the table below for an explanation of the symbols used to grade recommendations.

Strength of recommendation Symbol Level of evidence Symbol
Strong for intervention ↑↑ High ⨁⨁⨁⨁
Conditional for intervention Moderate ⨁⨁⨁◯
Neither intervention nor comparison Low ⨁⨁◯◯
Conditional against intervention Very low ⨁◯◯◯
Strong against intervention ↓↓

The authors also developed best practice statements for clinical care points that were considered self-evident or were not amenable to the GRADE process. The process was overseen by a project coordinator (see {publication} for details).

The opinions of clinicians and individuals with a lived experience of FRDA were sought in deciding the best repository and process of dissemination of the CMGs.

Individuals with Friedreich ataxia are considered at high risk of complications related to surgery and anesthesia due to comorbidities such as cardiomyopathy, scoliosis, diabetes and compromised lung function (1, 2). Cardiomyopathy is present in most individuals with Friedreich ataxia and left ventricular outflow obstructions should be avoided (1). The presence of scoliosis presents challenges for the use of central neuraxial blockade (1). In addition, concerns have been reported about the use of general anesthesia (3); however, the successful implementation of techniques such as combined spinal epidural anesthesia and total intravenous anesthesia have been reported (2, 4).

This chapter describes the particular surgical and anesthetic considerations relevant to individuals with Friedreich ataxia, focusing on monitoring cardiac function peri-operatively and managing the needs of individuals, both during and after surgery. In writing best practice statements and recommendations, the authors were tasked with answering the following questions:

5.1 Management strategies for monitoring cardiac function peri-operatively

5.2 Strategies for fluid and operative management – fluids

5.3 Strategies for fluid and operative management – early mobilization

5.4 Strategies for fluid and operative management – anesthesia