Anestesi pada penyakit langka

R6
 Achondroplasia

 Penyebab paling sering Dwarfism

 Autosomal dominant
 Mutasi FGFR3 receptor
 kepala besar, facial hypoplasia, spine deformation,
trident hand
 Achondroplasia & Anesthesia

 Kesulitan IV, mask ventilation, intubasi

 Risiko Cervical cord ischemia
 OSA
 Restrictive lung disease
 GERD
 kesulitan RA
 Angelman Syndrome
Happy Poppet Syndrome

 Mutation of UB3A gene, abnormal GABAR

 Developmental delay
 Movement dysfunction
 Minimal speech, nonverbal communication
 Microcephaly, seizures
 Prognathia
 Angelman & Anesthesia

 Dysregulation of GABA, NMDA, AMPA

 Difficult RA
 Bradycardia
 Syncope
 Seizure disorder
 Apert Syndrome
Acrocephalosyndactyly

 Malformation of the skull, hands, feet and face

 Mutation of fibroblast growth factor receptor 2 gene
 Craniosynostosis, Brachycephaly, mid -face
hypoplasia, Hypertelorism, increased ICP,syndactyly
 Cardiac defects, polycystic kidney, pyloric stenosis
 OSA, CSA
Apert Syndrome & Anesthesia

 Difficult IV
 Difficult mask ventilation
 High incidence of Bronchospasm
 No reported difficult intubations
 Might need CPAP post op
 Avoid sedatives and Opiods
Arthrogryposis Multiplex Congenita

 Intrauterine fetus joint contractures, 3 degrees of

severity
 Type 1 affects extremities
 Type 2 affects extremities + scoliosis+ CDH
 Type 3 affects CNS
Arthrogryposis Multiplex Congenita
& anesthesia

 Difficult IV
 Spinal and caudal might be difficult
 Possible cervical spine instability
 25% difficult intubation
 Difficult positioning for surgery
 Risk of bleeding if on Valproic acid
 Central core disease
Shy-McGee Syndrome

 Inherited dominant neuromuscular disorder=

congenital myopathy
 25% association with MH
 Hypotonia, motor developmental delay, with
predominantly proximal weakness
 Cardiomyopathy rare
 When associated with scoliosis echo and PFTs are
needed
Central core disease & Anesthesia

 MH avoidance technique (no Succinylcholine no

volatile anesthetics)
 TIVA and RA are safe
 Neurological consult before RA for Juridical reasons
 Pre-op CK level may be helpful
 Higher intr-aop blood loss during scoliosis surgery
 CHARGE Syndrome
Hall – Hittner Syndrome

 Coloboma
 Heart defect
 Atresia Choanae
 Retarded Growth and Development
 Genital Hypoplasia
 Ear Anomalies/Deafness
 Cleft lip and palate
 TEF
CHARGE Syndrome & Anesthesia

 Inhalation induction may be difficult

 RSI preferred
 Difficult intubation
 Risk of aspiration
 Risk of arrhythmias
 Prolonged post-op mechanical ventilation
 Duchenne muscular dystrophy
Dystrophinopathy

 Most common & severe muscular dystrophy

 Mutation in dystrophin gene on Chromosome Xp21
 Progressive skeletal muscle weakness
 Fatty and fibrous infiltration of muscles
 Age of diagnosis 3-5 years
 Risk of aspitation
 Cardiomyopathy (TEE)
 Duchenne muscular dystrophy &
Anesthesia

 GA with TIVA
 Prolonged muscle relaxant effects
 Avoid Succinylcholine and VA
 Risk of hyperkalemic cardiac arrest or sever
rhabdomyolysis
 No risk of MH short use of VA is possible
 Avoid NO2 in case of cardiac involvement
 RA can be done
 Epidermolysis bullosa

 Group of inherited diseases with trauma induced

blister formation of skin and mucosa
 Deficiency of structural proteins of the dermo -
epidermal junction
 Microstomia, ankyloglosson and dental decay
 Cardiomyopathy
 GERD
 Anemia
Epidermolysis bullosa & Anesthesia

 Difficult airway
 Prevent friction and trauma, lubrication of FM, LMA, ETT,
secure ETT with non adhesive
 LMA, ETT one seize smaller
 Extensive padding
 Infection prophylaxis
 Good pre-op sedation, RSI
 RA is OK but less skin infiltration with LA
 Patting the skin for disinfection
 Kasabach-Merritt Syndrome
Hemangioma-Thrombopenia

 Vascular lesion with consumptive coagulopathy and

throbocytopenia
 Vascular tumor with irregular nodules
 Pt on Steroids, Vincrstine, Interferon, Ticlopidine and
or Aspirin
 Avoid Platelet transfusion due to trapping in the
tumor
 Heart failure secondary to massive AV shunts
Kasabach-Merritt & Anesthesia

 Difficult airway
 No nasal intubation
 Avoid platelet transfusion
 Correct coagulopathy ( fibrinogen, tranexamic acid)
 Side effects from Chemotherapy
 RA (aware of thrombocytopenia)
 Mucolipidosis II and III

 Lysosomal storage disease

 Defective N –acetylglucosamine 1-phosphotransferase
 Accumulation of carbohydrate, lipids in various tissues and
organs
 The phenotype resemble Hurler Syndrome
 Jaw and neck may be stiff
 Short neck
 Thickened epiglottis, enlarged adenoids
 Cardiomyopathy, PHTN
Mucolipidosis II and III & Anesthesia

 Difficult airway , FOI

 Difficult LMA
 ETT smaller than predicted
 Difficult IV
 OSA
 Prader-Willi Syndrome
Prader-Labhardt-Willi Syndrome

 Genetic disorder of chromosome 15

 Hypothalamic-Pituitary abnormality
 Hypotonia in infancy, hyperphagia, morbid obesity
 Behavioral problems
 OSA
 Cardiomyopathy
 Seizure disorder
Prader-Willi Syndrome & Anesthesia

 Difficult airway management

 Difficult landmarks for RA
 Difficult IV
 High risk for bronchospasm
 High risk for aspirtation
 Potential for prolonged effects of NMB
 Safe to use succinylcholine
 Ketamine can be use with caution
 Russel - Silver Syndrome
Russel - Silver Dwarfism
 Genetic etiology of chromosome 7 and 11p15
 Growth retardation
 Face and limb asymmetry
 Relative macrocephaly prominent for-head
 Hypospadias
 Anterior and small larynx
 Subglottic stenosis
 Retrognathia and hypognathia
 Risk of hypoglycemia
 Russel - Silver Syndrome &
Anesthesia

 Difficult airway due to facial dysmorphysm,

retrognathia, hypognathia, small mouth opening,
 Difficult mask ventilation
 RA can be used
 Ambulatory surgery is not recommended
 Welander Distal Myopathy
distal myopathy Swedish type

 Autosomal dominant
 Almost exclusively found in Sweden and Finland
 Late adult onset
 Weakness and atrophy of distal muscles
 Inability to extend the fingers
 Decreased DTR
 No cardiac involvement
 Welander Distal Myopathy &
Anesthesia

 GA and RA not contraindicated

 PT with RLS no Etomidate or Propofol
 Careful use of NMB
 Prolonged Q-T Interval Syndrome
Jervell and Lange-Nielsen Syndrome
Romano-Ward Syndrome
 It can be congenital or acquired
 Causes of acquired are :Quinidine, Disopyramide, TCA,
SAH, hypokalemia, hypomagnesaemia, right neck
dissection
 The pathognomonic feature is prolonged Q-T more
than 0.44 sec on EKG even when corrected for HR
 Can present as Syncope, or sudden death due to VT
 Asymmetric sympathetic innervation of the right and
left heart
Prolonged Q-T and Anesthesia

 BB can shorten QT interval

 Left stellate ganglion block can transiently shorten Q-T for
acute cardiac arrhythmias
 Surgical Ganglionectomy is successful if the block work
 EKG pre-op for children with congenital deafness or Hx of
sudden death in the family
 GA might trigger ventricular Dysrhythmias if not on BB pre-
op
 Electrical defibrillator should be available
 Phenytoin can shorten Q-T can be given po after surgery
Malignant Hyperthermia
coexisting diseases
 AT A GLANCE...
 Epidemiology of MH • Mimics of MH
 Pathogenesis of MH • Diseases Associated with MH
 4 Different Case • Possibly MH-Related
Scenarios • Rhabdomyolysis but not MH
 The MH Clinical • Muscle Biopsy & IVCT
Grading Scale • MHAUS, NAMHR, NMSIS
 MH-like Anesthetic & MH Hotline
Events
• Bibliography
“Epidemiologic barriers” in defining the
true incidence of MH”

 Difficulty in establishing diagnosis of MH

 No noninvasive diagnostic screening test
“Epidemiologic barriers” in defining
the true incidence of MH” (cont.)

 All cases are not reported to MH Registry

 Triggering of MH in susceptible patients may not occur
 Lack of uniform criteria for MH diagnosis
 Incidence of Different Forms of MH
in Relation to Type of Anesthesia
Fulminant MH Abortive MH Overall incidence
(all subgroups of suspected MH
included)
Total number of anesthetics 1:251,063 1:17,435 1:16,303

General anesthesia 1:221,811 1:15,404 1:14,403

Anesthesia with potent

inhalation agent 1:84,488 1:6,653 1:6,167

With succinylcholine 1:61,961 1:4,506 1:4,201

Without succinylcholine 1:174,597 1:20,541 1:18,379

Anesthesia with administration of

succinylcholine 1:140,006 1:8,819 1:8,297
 Pathogenesis: Key Concepts

Heterogeneous disorder
Genetically transmitted with variable
expression/penetrance
Can be triggered by volatile
anesthetics and succinylcholine
 Hereditary - multiple genes
Several chromosomes:
 19q11.2-13.2 Ryanodine (RyR1)
 Release of Ca2+ stores from sarcoplasmic reticulum
 17q11.2-q24
 Altered sodium channel functioning
 7q21.1
 Dihydropyridine (DHP), voltage sensor for RyR1
 1q32
 CACNL1A3 gene encoding the alpha 1-subunit of the voltage-
gated DHP receptor that interacts with RyR1
Non-specific clinical presentation

 Hypercarbia
 Tachycardia
 Fever
 Hyperventilation
 Metabolic and Respiratory Acidoses
 Cardiovascular collapse
 Rhabdomyolysis
Process Indicator Points
1. Rigidity Click for larger picture
Generalized muscular rigidity
Masseter spasm________________________________
15
15
2. Muscle Breakdown Creatine Kinase >20,000 IU after succinylcholine 15
Creatine Kinase >10,000 IU with no succinylcholine 15
Cola colored urine in perioperative period 10
Myoglobin in urine > 60 mcg/L 5
Myoglobin in serum > 170 mcg/L 5
Blood/plasma/serum K> 6 mEq/L no renal ills _____ 3
3. Respiratory Acidosis PETCO2 > 55 mmHg with controlled ventilation 15
Arterial PaCO2 > 60 mmHg, controlled ventilation 15
PETCO2 > 60 mmHg with spontaneous ventilation 15
Arterial PaCO2 > 65 mmHg, spontaneous ventilation 15
Inappropriate hypercarbia, Anesthesiologist’s call 15
Inappropriate tachypnea__________________________ 10
4. Temperature Increase Inappropriately rapid increase 15
Inappropriately increased temperature > 38.8C_______ 10
5. Cardiac Involvement Inappropriate sinus tachycardia 3
Ventricular tachycardia or fibrillation_________________ 3
6. Family History Positive family history in first degree relative 15
Positive family history, more distant relative ____ 5
7. Others Arterial base excess more negative than –8 mEq/L 10
Arterial pH <7.25 10
Rapid reversal of MH signs after iv dantrolene 5
Positive MH family history with another indicator from the
patient’s anesthetic experience other than increased CK 10
Elevated CK and a family history of MH______________ 10

Larach MG, Et Al, MH Clinical Grading Scale, Anesthesiology 1994; 80:771-9

CGS Sum and Probability of MH

20-34 Somewhat greater

than likely

35-49 Very likely

>50 Almost certine

 Clinical Grading Scores (CGS)
Case 1 Case 2 Case 3 Case 4
Rigidity 0 0 15 15
Muscle Injury 15 15 15 0
Respiratory 0 15 0 15
Temperature 10 0 0 15
Cardiac 3 0 0 15
Family History 0 0 0 0
Other 10 5 0 0
SUM 38 35 30 45
 MH-Like Anesthetic Events

MYOPATHY INCIDENCE AGE at Dx

Duchenne 0.0020 5 (<16) yrs

Becker 0.00036 12 (4-19)

Myotonia 0.000135 < 14 years

Dystrophica
 Differential Diagnosis

Thyrotoxicosis Pheochromocytoma
MH
 ETCO2 +++ ++ ++
 HR +++ +++ +++
 BP + ++ +++
Rigidity ++ +/- -
Acidosis +++ - +
 Some Mimics of MH

 Adverse drug reactions  Cystinosis

 Arthrogryposis  Glycogen storage disease
 Carnitine palmitoyl  Lymphoma
transferase deficiency  Mitochondrial disease
 CNS diseases  Neuroleptic malignant
 Contrast media in CSF syndrome
 Viral myopathy
 Elevated ETCO2 with
laparoscopic cases  William’s syndrome
 Diseases Associated with MHS

 Central core disease

 Isolated elevation of creatine kinase
 King Denborough syndrome
 Possibly MH Related

 Dystrophinopathy
 Emery Dreifuss MD
 Fascio-Scapulo-Humeral MD
 Abnormal Muscle Enzymes
 Ion Channel Mutations
 Na, K, Cl
 Rhabdomyolysis, but NOT MH

 Brody’s disease
 Deficient calcium adenosine triphosphatase
 Mc-Ardle’s disease
 Myophosphorylase B deficiency
 Muscle Biopsy and IVCT

Nearly 100%
sensitive

85% specific
 Anesthesia for MH Susceptible
Patients

 If your patient has had a muscle biopsy for MH contracture

testing or is registered through the North American Malignant
Hyperthermia Registry (NAMHR):
 Call # 888-274-7899
 Complete & return report of anesthetic
 Bibliography
1. Larach, MG for the North American Malignant Hyperthermia
Group. Standardization of the caffeine-halothane muscle
contracture test. Anesth Analg 1989; 69:511-515
2. Laboratory diagnosis of malignant hyperpyrexia susceptibility
(MHS). European MH Group. Br J Anaesth. 1985; 57(10):1038.
3. European Malignant Hyperpyrexia Group. A protocol for the
investigation of malignant hyperpyrexia (MH) susceptibility. Br
J Anaesth, 1984; 56: 1267-1269.
4. Allen, G, et al. The sensitivity and specificity of the caffeine-
halothane contracture test. Anesthesiology 1998; 88:579-88.
5. Ording, H., et al. In-vitro contracture test for diagnosis of
malignant hyperthermia following the protocol of the
European MH Group: results of testing patients surviving
fulminant MH and unrelated low-risk subjects. The European
Malignant Hyperthermia Group. Acta Anesthesiol. Scand., 1997;
41: 955-966.
 Bibliography, cont.
6. Urwyler A., et.al. Guidelines for molecular genetic dectection of
susceptibility to malignant hyperthermia. And editorial III. Br J
Anaesth. 2001; 86(2): 283-7.
7. Brandt, A., et al. Screening of the ryanodine receptor gene in 105
malignant hyperthermia families: novel mutations and concordance
with the in-vitro contracture test. Hum. Mol. Genet. 1999; 8: 2055-
2062.
8. Brown, R., et al. A novel ryanodine receptor and genotype-
phenotype correlation in a large malignant hyperthermia New
Zealand Maori pedigree. Hum. Mol. Genet. 2000; 9: 1515-1524.
10. Larach, MG, et al. MH Clinical Grading Scale. Anesthesiology 1994;
80:771-9.
11. Ording, H. Incidence of Malignant Hyperthermia in Denmark.
Anesth Analg 1985; 64:700-4.
12. Benumof, Jonathan. Muscle Diseases. Anesthesia &
Uncommon Diseases. (4/e), Philadelphia, 1998.
 Bibliography, cont.
.
13. Monnier N, et al. Malignant Hyperthermia susceptibility is associated
with a mutation of the alpha 1 subunit of the human dihydropyridine-
sensitive L-type voltage-dependent calcium channel receptor in skeletal
muscle. Am J Hum Genet 1997;60(6):1316-25.
14. Tobin JR, Jason DR, Nelson TE, Sambuughin N. Malignant Hyperthermia
and Apparent Heat Stroke, JAMA 2001; 286(2):168-169.
16. Larach, MG, et al. MH Clinical Grading Scale. Anesthesiology 1994; 80:771-
9.
17. Dierdorf, Stephen. Anesthesia for Patients with Rare and Coexisting
Diseases. Clinical Anesthesia (3/e), Philadelphia, 1996. p 461.
18. McPherson EW, Taylor CA Jr. The King Syndrome: MH, myopathy, and
multiple anomalies. Am J Med Genet 8:159, 1981.
19. Loke JC, MacLennan DH. Bayesian modeling of muscle biopsy
contracture testing for malignant hyperthermia susceptibility.
Anesthesiology 1998;88(3):589-600.