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]