REVIEW OF MANUSCRIPT
The authors’, while seemingly well-intentioned and methodical, have made a number of concerning errors (Fig 1), all of which could have been avoided by a more careful search of recent literature on FBS. For example, the authors omitted the two seminal articles that defined the clinical and genetic diagnosis,[16-17] molecular physiology,[18-20] the only meta-analysis on FBS,[3] and the clinical practice recommendations for anesthesia care.[8] Unfortunately, the authors cite[1-2] only one recent article, which was one of four published over the past year that were deeply flawed[10] and to which we responded[13] in a letter to the editor. Conducting a sound literature search is not restricted to the preserve of academics. The present article in question[1-2] brings into sharp relief the connection between the quality of a literature search and clinical reasoning displayed in patient care.
The authors cite[1-2] the unsubstantiated frequency of 1:1 million, which was based on a single retrospective study of patients in the UK having skeletal dysplasias and included FBS.[21] FBS is often misdiagnosed, making it academically irresponsible to accept a recorded FBS diagnosis without objective patient data.[3] This study’s frequency for FBS is no longer accepted, and the prevailing estimate is that 200-300 individuals worldwide may have FBS.[4]
The authors describe patients as having, “multiple joint contractures, characteristic facial features, such as microtia, defects of the hands and feet, such as clubfoot, and skeletal malformations.”[1-2] External ear position variances may be seen in FBS, but microtia is not seen in FBS.[3] Otherwise, the description is mostly true for most patients, while remaining very misleading. Only the craniofacial features (microstomia, pursed whistling lips, deep nasolabial folds, and H or V-shaped chin defect) required in the diagnostic criteria are pathognomonic for FBS.[3,16-17] Distal extremity contractures are a non-diagnostic finding in FBS and common in many syndromic and non-syndromic entities.[3-4,16] The authors also do not state[1-2] the accepted clinical diagnostic criteria[16] that have been shown to be strongly correlated with molecular diagnosis[17]. Not directly stating the diagnostic criteria, as the authors failed to do,[1-2] can confuse the reader unfamiliar with FBS.
Furthermore, FBS is a congenital craniofacial syndrome of myopathic origin that frequently involves findings outside the craniofacial region (spine and extremities), though FBS has had many classifications since its first description in 1938 and independent confirmation in 1962.[22-24] In the syndrome, “skeletal malformations” are secondary effects of the primary myopathic process of fibrose tissue replacement of normal muscle fibers.[4] This fibrose tissue acts as constricting bands, the way collagen behaves in severe burns.[4] These findings are consistent with in vitro molecular myophysiology observations showing problems with the metabolic process for contraction and extreme muscle stiffness that reduces muscular work and power.[18-20] Misunderstanding of etiology in FBS has led to inappropriate treatment plans, especially surgeries, and has resulted in tragic, lifelong impairments.[3-5]
The authors referred to a risk of, “association with malignant hyperthermia (MH),” and FBS.[1-2] The potential association of MH and FBS was based on a single report of two cases.[25] Some patients with FBS do, indeed, develop hyperpyrexia during general anesthesia, but it has also been observed to be resolved by administration of ibuprofen.[8] These hyperpyrexia events, which may include tachycardia and increased muscle rigidity, have also been seen in settings where an MH protocol was followed and in non-operative stress situations, such as physical or mental stress well beyond what the individual typically experienced.[8] It seems, then, these hyperpyrexia events may not represent true MH events.[8]
The authors write that, “Reports on the general anesthetic management of FSS patients have been disorganized.”[1-2] While it is true that anesthesia case reports have been spotty and of varying quality, this is not a unique phenomenon.[3] There are only two published studies of FBS, neither of which addressed anesthesia in any detail.[16-17] There is, however, a meta-analysis of individual patient data extracted from rigorously evaluated case reports and anesthesia clinical practice recommendations.[3,8] Both of these articles consolidate the evidence-base for anesthesia care of FBS patients in detail.[3,8]
Without photographs or a detailed description of how the patient met the diagnostic criteria, it is not certain the patient described had FBS. Stating the patient had FBS is insufficient, considering the false positive rate may be between 30-60%.[3] Near the end of the article, the authors remark that, “There was no facial deformity… in this case,”[1-2] making it rather unlikely the patient described had FBS. Four main craniofacial deformities (microstomia, pursed whistling lips, deep nasolabial folds, and H or V-shaped chin defect) are required for diagnosis,[3,16-17] and all patients present with an assortment of additional common but not required craniofacial stigmata.[3,6]
The authors assert that general anesthesia would cause, “worsening of respiratory insufficiency and postoperative pneumonia.”[1-2] Though the risk is greater for post-operative respiratory complications in FBS patients, general anesthesia certainly does not directly cause post-operative respiratory distress and pneumonia.[8] Nonetheless, patients require care from experienced providers, ideally in tertiary referral centers.[8] Astute anesthesia and post-anesthesia care for patients with FBS, as outlined in the clinical practice recommendations, is specifically directed toward avoiding post-operative respiratory sequelae.[8]
The authors considered four options: local anesthesia, local anesthesia with narcotic analgesia, local anesthesia with sedation, and general anesthesia.[1-2] Expressly because of the need to ensure a secure airway to prevent aspiration pneumonia, the two safe options are local anesthesia only, where the patient is fully alert without impaired cognition and able to protect their own airway; and general anesthesia, where the patient’s airway is secured via orotracheal intubation or a surgical airway.[7-8] The authors acknowledged the pulmonary concerns[1-2,26] but paradoxically wished to avoid invasive airway management in a sedated patient undergoing oral surgery, which is a major risk to patient safety in FBS and should not happen.[1-2] Local anesthesia with narcotic analgesia would not be an option either. As correctly observed by the authors, respiratory depression can be exacerbated with opiates, but short-acting options exist and have been safely used in this syndrome.[8] The bigger risk is the cognitive effect of the narcotics when used in an awake FBS patient for procedural pain control for oral surgery.[7-8]
The authors next outline three concerns they have with general anesthesia, including: difficult intubation, “respiratory failure”, and risk of MH.[1-2] They seemingly present these as justification for considering general anesthesia to be contraindicated in FBS or at least in their case.[1-2] Difficult intubation is a major challenge in FBS requiring considerable skill but is not insurmountable.[8] The other two concerns are flatly illogical. “Respiratory failure” should never be a likely event with good care.[8] Respiratory depression is a greater concern in FBS but as described above, one of the major goals of anesthesia care is to prevent it.[8] As mentioned above, MH is not associated with FBS.[8]
The authors write, “[FBS] causes respiratory decline in adults.”[1-2] There is no evidence supporting either a decline in respiratory function or of FBS being a primary cause in any decline observed. While FBS may limit healthy physical activity necessary for maintaining respiratory function status, lifestyle and ageing are expected to be main contributors to any observed decline, as they would be in the general population.[5] The authors also refer to, “respiratory muscle fatigue.”[1-2] As discussed previously, FBS results in the formation of white fibrous tissue constricting bands within normal muscle and complete muscle replacement by white fibrous tissue.[4] Primary muscle fatigue is not part of FBS.
Finally, the authors consider nasal high-flow (NHF) oxygen cannulae in FBS and write, ““Although NHF was not used in this case, it may have been useful….”[1-2] Though NHF has an important role in critical care and other settings, its use in this patient population probably would be impractical, due to anatomically restricted airflow in the nasopharynx of most FBS patients that would preclude efficient oxygenation. For this reason, nasal airways and nasal intubation also are ineffective airway management methods in many FBS patients. Orotracheal intubation or a surgical airway are the most reliable techniques for providing effective airway protection and positive-pressure support.[8]