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Lesch-nyhan syndrome
is associated with neurological, cognitive and behavioral disturbances. This
syndrome has several problems such as positioning and difficult intravenous
cannulation. These patients are prone for bradycardia, pulmonary aspiration, convulsion
and sudden death. Anesthetic implications are not well described in these
patients due to the low incidence of the disease.
This article’s
objective is to systematically review these needs in the perioperative period
and how to approach them.
To conclude,
patients with Lesch-nyhan syndrome should be carefully evaluated in the
perioperative period and vigilant monitoring is required.
INTRODUCTION
Lesch-Nyhan syndrome is a rare X-linked recessive disorder with a
prevalence of 1:380000 caused by the deficiency of hypoxanthine-guanine
phosphoribosyltransferase (HGPRT) enzyme resulting in overproduction of purine
and the accumulation of uric acid [1]. The syndrome almost always affects
males, with very few cases reported in females [2]. The clinical features of
Lesch Nyhan syndrome depends on whether there is complete or partial HPRT
deficiency resulting in classical LND syndrome or a phenotype with some features
absent or attenuated. Collectively, these patients are labeled as LND variants
[3].
The classical clinical manifestations are characterized by neurological,
cognitive and behavioral disturbances, congenital insensitivity to pain and
uric acid overproduction. The most common presenting feature is developmental
delay during the first year of life, with hypotonia and delayed motor skills
usually evident by three to six months of age [1]. Affected children develop
action dystonia (classical feature), choreoathetosis, opisthotonos and
sometimes ballismus [4]. They also develop signs of pyramidal involvement
including spasticity, hyperreflexia and extensor plantar reflexes [1]. Almost
all affected individuals develop persistent self-injurious behavior between 1 to
3 years of age, a hallmark of the disease [5]. Self-injury most often involves
biting of the fingers, hands, lips and cheeks [6]. Other compulsive behaviors
may include aggressiveness, vomiting, spitting and coprolalia [1].
Hyperuricemia is associated with nephropathy, urinary tract calculi, arthritis,
tophi. So these children may present for urinary tract, orthopedic surgeries or
any unrelated surgical problems [2]. EEG may show nonspecific changes of
slowing or disorganization.
There will be nonspecific changes of atrophy in the central nervous
system with reduced cerebral volume and reduced caudate nucleus volume in CT
and MRI scans. The findings of MRI revealed reduced basal ganglia volume which
is consistent with the dystonic movement disorder [7].
METHODS
A search was performed on PubMed and Cochrane database using the
following keyword combinations “lesch-nyhan syndrome”, “anesthesia” and
“surgery”, “preoperative”, “postoperative”. 14 articles were selected from this
revision. Inclusion criteria of the study were written in English, a systematic
revision, case reports and case study. Only pediatric population was accepted
in the group. Relevant papers cited in the selected article were added to the
group ending up with 20 articles being analysed in this review.
ANESTHETIC
IMPLICATIONS
The anesthetic considerations in Lesch-Nyhan syndrome are because of the functional disturbances
created by the
The main anesthetic concerns are:
1. Difficult
Intravenous access
2. Difficult
airway
3. Positioning
4. Risk
of aspiration
5. Bradycardia,
apnea and sudden death
Preoperative evaluation should be done with thorough history
and examination to assess self-mutilating behavior, aggressiveness,
developmental milestones, previous anesthetic exposure, cognitive dysfunction,
difficult airway, spasticity, venous access, heart rate, blood pressure,
sensory and motor functions, power and reflexes. Any other associated
gastrointestinal disorders, respiratory, renal impairment, seizures, macrocytic
anemia, malnourishment, arthritis, gouty tophi should be noted. Laboratory
investigations like complete blood count to look for megaloblastic anemia,
serum electrolytes, renal function tests and serum uric acid levels and
ultrasound examination to rule out renal abnormalities, ECG to look for rhythm
disturbances, chest x-ray are needed.
These children may present for urinary tract, orthopedic
surgeries, dental extraction or any unrelated surgical problems. There are very
few case reports of anaesthesia for a case of lesch-nyhan syndrome due to its
rare incidence.
The patients with Lesch-Nyhan Syndrome have several problems
like positioning in operating room, difficult intravenous cannulation and
difficult airway because of the spasticitiy [8]. Also, these patients are at
risk of bradycardia, pulmonary aspiration, convulsion and sudden death, and an
increased incidence of vomiting.
The choice of anesthetic agents depends on the preoperative
assessment, surgical problem, degree of metabolic dysfunction and renal
function. Patients should be premedicated with metoclopramide to enhance
gastric emptying and also use of H2 receptor blocker to increase the
gastric pH to 2.5 as the children are more prone for vomiting and aspiration
pneumonia due to athetoid dysphagia which is characteristic in the syndrome
[8].
Benzodiazapine like midazolam (oral or intravenous) which is
most commonly used in pediatrics can be given to premedicate the child before
induction to alleviate the anxiety [9]. The metabolisms of thiopental, ketamine
or etomidate are not affected by reduced HGPRT function. Propofol is the
preferred induction agent in such children10. The advantages of propofol
include the ease of titration to anesthetic depth, antiemetic properties of the
drug reduces the incidence of vomiting and may help in preventing aspiration
[11]. It also increases urinary uric acid excretion and is beneficial for such
patients [12]. Metabolism of most of the commonly used inhalational agents is
not affected. Isoflurane is the preferred agent due to absence of
nephrotoxicity [13]. Succinylcholine is preferably avoided because of abnormal
potassium influx due to spastic muscle disorder [14]. Atracurium is safe for
muscle relaxation [15]. Abnormalities of adrenergic responses, reduced
monoamine oxidase activity have been reported [2]. The potential for
bradycardia and heart block exists during the induction of anesthesia with
propofol in any patient. Synergy of this reaction with the cholinergic
predominance of the patient with LNS during stress may occur due to the absence
of adrenergic response to stress [16,17]. Exogenous catecholamine should be
administered carefully. A case report published by Reddy et al. [9] reports
that there was decreased anesthetic requirement throughout the procedure and
there was delayed recovery for 15 min. In this case, child had episodes of
apnea during recovery when there were occasional ectopics and bradycardia which
responded to injection atropine. So careful titration of drugs and vigilant
intraoperative monitoring is required to prevent intraoperative complications.
The self-mutilation causes trauma to perioral tissues and
subsequent scarring may suggest difficulties in endotracheal intubation [8]. A
case report published by Salhotra et al. [18] reports the rare occurrence of a
tracheal diverticulum associated with Lesch-Nyhan syndrome in an 11 year old
boy. During induction of general anesthesia, unexpected difficult intubation
was encountered with a 6.5 mm ID endotracheal tube and successively smaller
tubes, also failing to pass 1 cm beyond the vocal cords. Intubation was finally
successful with a 4.5 mm ID tube [18]. Difficult airway equipment and smaller
size endotracheal tubes should be kept ready for such cases. Intraoperative reduced
requirement of analgesics have been noted in these cases due to congenital
insensitivity to pain [9].
Perioperative proper positioning, use of protective padding
and avoidance of contact with hard surfaces are the protective precautions to
avoid direct pressure on susceptible skin and peripheral nerves [19]. Careful
positioning of the patient with proper supporting can reduce, but may not be
eliminate injuries to peripheral nerves [20]. Anesthesiologist should be
familiar with the anatomical traces of the peripheral nerves to prevent
pressure injury during the surgical procedure.
During extubation and recovery, these patients should be
extubated after they have adequate spontaneous respiration and awake extubation
is preferred due to difficult airway and monitored in the postoperative
recovery till complete recovery from anesthesia as these children are more
prone for respiratory compromise, convulsions and sudden death.
CONCLUSION
In conclusion, preoperative evaluation should be done to look
for airway difficulty, body posture, difficulty in positioning, venous access,
behavior, degree of developmental delay and other associated abnormalities.
Anesthesia should be administered in slow and titrated doses. Necessary
precautions should be taken to prevent vomiting and aspiration. Careful
positioning with padding of the pressure points to prevent pressure injuries.
Vigilant intraoperative as well as postoperative monitoring in the recovery as
these children is more prone for convulsions, respiratory compromise and sudden
death. Even though there are many contraindications to the standard anesthetic
techniques for children with Lesch-Nyhan syndrome, anesthetic management should
be individualized depending on the associated abnormalities and taking the basic
precautions.
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