Anesthesia for Rare Co-existing Diseases

Alexandru Apostol, M.D.

The most common cause of Dwarfism Autosomal dominant Mutations of FGFR3 receptor Large head, facial hypoplasia, spine

deformation, trident hand

Achondroplasia

Difficult IV, mask ventilation, intubation Risk for Cervical cord ischemia OSA, CSA, PHTN Restrictive lung disease GERD Difficult RA

Achondroplasia & Anesthesia

Mutation of UB3A gene, abnormal GABAR Developmental delay Movement dysfunction Minimal speech, nonverbal communication Microcephaly, seizures Prognathia

Angelman SyndromeHappy Poppet Syndrome

Dysregulation of GABA, NMDA, AMPA Difficult RA Bradycardia Syncope Seizure disorder

Angelman & Anesthesia

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 SyndromeAcrocephalosyndactyly

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

Apert Syndrome & Anesthesia

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

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

Arthrogryposis Multiplex Congenita & anesthesia

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 diseaseShy-McGee Syndrome

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

Central core disease & Anesthesia

Coloboma Heart defect Atresia Choanae Retarded Growth and Development Genital Hypoplasia Ear Anomalies/Deafness Cleft lip and palate TEF

CHARGE SyndromeHall – Hittner Syndrome

Inhalation induction may be difficult RSI preferred Difficult intubation Risk of aspiration Risk of arrhythmias Prolonged post-op mechanical ventilation

CHARGE Syndrome & Anesthesia

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 dystrophyDystrophinopathy

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

Duchenne muscular dystrophy & Anesthesia

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

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

Epidermolysis bullosa & Anesthesia

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 SyndromeHemangioma-Thrombopenia

Difficult airway No nasal intubation Avoid platelet transfusion Correct coagulopathy ( fibrinogen,

tranexamic acid) Side effects from Chemotherapy RA (aware of thrombocytopenia)

Kasabach-Merritt & Anesthesia

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

Difficult airway , FOI Difficult LMA ETT smaller than predicted Difficult IV OSA

Mucolipidosis II and III & Anesthesia

Genetic disorder of chromosome 15 Hypothalamic-Pituitary abnormality Hypotonia in infancy, hyperphagia, morbid

obesity Behavioral problems OSA Cardiomyopathy Seizure disorder

Prader-Willi SyndromePrader-Labhardt-Willi

Syndrome

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

Prader-Willi Syndrome & Anesthesia

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 SyndromeRussel - Silver Dwarfism

Difficult airway due to facial dysmorphysm, retrognathia, hypognathia, small mouth opening,

Difficult mask ventilation RA can be used Ambulatory surgery is not recommended

Russel - Silver Syndrome & Anesthesia

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 Myopathydistal myopathy Swedish type

GA and RA not contraindicated PT with RLS no Etomidate or Propofol Careful use of NMB

Welander Distal Myopathy & Anesthesia

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 Interval Syndrome

Jervell and Lange-Nielsen Syndrome

Romano-Ward Syndrome

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

Prolonged Q-T and Anesthesia

Malignant Hyperthermia coexisting diseases

AT A GLANCE...

Epidemiology of MH Pathogenesis of MH 4 Different Case

Scenarios The MH Clinical

Grading Scale MH-like Anesthetic

Events

• Mimics of MH• Diseases Associated with MH

• Possibly MH-Related• Rhabdomyolysis but not MH

• Muscle Biopsy & IVCT• MHAUS, NAMHR, NMSIS

& MH Hotline• 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 disorderGenetically 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

Case One in PACU

A 13 year old boy underwent

2 hours of uncomplicated General Anesthesia.

Case Two in OR

A 10 year-old male was given Propofol & Rocurronium to facilitate tracheal intubation. Anesthesia wascontinued with Isoflurane/N2O.

Case Three Masseter Rigidity?

A 16 year-old male who refused spinal anesthesia for lower extremity surgery, was given Propofol and Succinylcholine (no Volatile Anesthetic gas).

Case Four Outside

A 12 year old male collapsed after rigorous exercise.

Tobin JR, Jason DR, Nelson TE, Sambuughin. Malignant Hyperthermia and Apparent Heat Stroke N. JAMA 2001; 286(2):168-169 http://jama.ama-assn.org/issues/v286n2/ffull/jlt0711-4.html

Process Indicator Points1. Rigidity Generalized muscular rigidity 15

Masseter spasm________________________________ 152. Muscle Breakdown Creatine Kinase >20,000 IU after succinylcholine 15

Creatine Kinase >10,000 IU with no succinylcholine 15Cola colored urine in perioperative period 10Myoglobin in urine > 60 mcg/L 5Myoglobin in serum > 170 mcg/L 5Blood/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 15Inappropriate tachypnea__________________________ 10

4. Temperature Increase Inappropriately rapid increase 15Inappropriately increased temperature > 38.8C_______ 10

5. Cardiac Involvement Inappropriate sinus tachycardia 3Ventricular 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 10Arterial pH <7.25 10Rapid reversal of MH signs after iv dantrolene 5Positive MH family history with another indicator from the patient’s anesthetic experience other than increased CK 10Elevated CK and a family history of MH______________ 10

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

 Click for larger picture

CGS Sum and Probability of MH

Almost certine>50

Very likely35-49

Somewhat greater than

likely

20-34

Clinical Grading Scores (CGS)

45303538 SUM

0 0 510Other

0 0 0 0Family History

15 0 0 3Cardiac

15 0 010Temperature

15 015 0Respiratory

0151515Muscle Injury

1515 0 0Rigidity

Case 4

Case 3

Case 2

Case 1

MH-Like Anesthetic Events

< 14 years 0.000135 Myotonia Dystrophica

12 (4-19) 0.00036 Becker

5 (<16) yrs 0.0020 Duchenne

AGE at DxINCIDENCEMYOPATHY

Differential Diagnosis

+-+++Acidosis

-+/-++Rigidity

++++++ BP

+++++++++ HR

+++++++ ETCO2

Pheochromocytoma

ThyrotoxicosisMH

Some Mimics of MH

Adverse drug reactions Arthrogryposis Carnitine palmitoyl

transferase deficiency CNS diseases Contrast media in CSF Elevated ETCO2 with

laparoscopic cases

Cystinosis Glycogen storage

disease Lymphoma Mitochondrial disease Neuroleptic

malignant syndrome Viral myopathy 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

Bibliography1. 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.