9/30/2020 Anesthesia Implications of Muscular Dystrophy

Daniel Edrich MD
Enrique Pantin MD

Transcript

1. Anesthesia Implications of Muscular Dystrophy Daniel Edrich MD Enrique Pantin MD
2. CASE 1 61y M, 72.5kg, 71in PMH • Non-insulin dependent Dm • HDL • COPD • Muscular dystrophy ** • Ventilator dependent • Wheelchair bound • Chronic cholecystitis • (wife does not recall if his previous procedures were done with TIVA or inhaled anesthetics) Allergies - Sonata -Tetracycline PSH - Tracheostomy - PEG - Percutaneous cholecystostomy - Femur ORIF - Tonsillectomy/adenoidectomy [1999]
3. Pt. Medications • Enoxaparin • Ipratropium • Metformin • Montelukast • Omeprazole • Simvastatin • Tamsulosin • Dexamethasone • Triamterene- HCTZ • Tobramycin • Tradjenta • pioglitazone
6. PLAN?
8. • Anesthesia start time 18:49 • Surgery start time 19:27 • Surgical end time 21:05 • Anesthesia end time 21:25
9. Chapter 13 Time of the Day Crucial interval 6pm- 6am Precipitous drop in staff numbers High frequency of case handoffs Maximal accumulated decline of cognitive function during wakefulness Falling body temperatures and increased reaction times
12. This pt. presented 1 week later febrile (101F) with CT scan showing a gall bladder fossa abscess. He subsequently underwent a percutaneous IR drainage and started on empirical antibiotic therapy
13. Additional case • 14 year old Male • Presents with complaints of gradual fatigue and weakness – "difficulty opening bottles and lifting things” • Loss of appetite and 20lb weight loss • Daily Fevers – attenuated with Tylenol and ibuprofen • NO surgical hx, mother denies family hx and any other significant pmh • Born FT/NVD • Pt to undergo go a muscle biopsy, bone marrow biopsy, lymph node biopsy Labs: NKDA No CP/SOB
14. • Echo- moderate to sever pulmonary hypertension • Mild to moderate dilated RV • Good LV function • No structural defects • Moderate pericardial effusion • Mild TR • ECG: sinus brady • Ldh: 866. [125-220] • CPK: 4772, 5389. [25-210] • Tropinins: 1.08, 1.0. [<0.02] • CKMB: 91.5, 83.6, 103.8 [0-6.3] • AST: 259. [10-55] • ALT: 156. [10-50] • Aldolase: 52, 38.5, 59.6. [< 14.5] • INR 1.28, PTT 31, PT 15.1
16. Muscular Dystrophy Inherited disorders of painless muscular degeneration and atrophy Symmetric skeletal muscle weakness/wasting without denervation (sensation and reflexes are intact) Mutation prevents normal formation of dystrophin, a muscle stabilizing protein Leading to complete loss of dystrophin or a partially functional dystrophin protein that disrupts sarcolemma integrity leading to myofibril atrophy, necrosis, and fibrosis. Most prevalent subtypes -- Duchenne’s and Becker’s Proximal deep tendon reflexes in the upper extremities and patella may disappear despite lack of denervation -tendo Achilles reflex remains intact even in later stages of the disease
17. • Dystrophin and dystrophin associated glycoprotein ( DAG) is responsible of muscle membrane integrity- despite the fact that it accounts for only approximately 0.002% of the protein in striated muscle • Lack of dystrophin leads to cellular and membrane instability, with progressive leakage of intracellular components an elevation on creatine phosphokinase • Eventually damaged muscle cells are invaded by macrophages and cytotoxic T cells and destroyed subtypes
18. A. Duchenne type and Becker Type B. Emery-Dreifuss Type C. Limb girdle Type D. Facioscapulohumeral Type E. Distal Type F. Oculopharyngeal Type Distribution of muscle weakness Key: Limb girdle Oculopharyngeal Emery-Dreifuss Duchenne type and Becker Type Facioscapulohumeral Distal
19. DMD vs BMD Duchenne’s muscular dystrophy • X- linked recessive • Incidence 1:3500 live births • Complete loss of dystrophin • Presents in childhood – around 4 years of age – often with delayed walking – usually around 18m or later Becker’s muscular dystrophy • X- linked recessive • Incidence 1:18000 live births • partially functional dystrophin protein • Presents with muscle weakness in adolescence
20. Genetics • Defect occurs on the short arm of the X chromosome at the Xp21 region- which contains the gene for Dp427 ( dystrophin) • Deletion is the most common form of mutation in the dystrophin gene • Because of the large size of the gene new mutation are common and account got 1/3 of new cases (2500 kilobases long)
21. Was only able to find one note with the subtype of muscular dystrophy of presented Pt • Facioscapulohumeral muscular dystrophy (FSHD) • FSHD is the third most common type of muscular dystrophy, behind Duchenne and Becker muscular dystrophies • The estimated prevalence of FSHD about 4 cases per 100,000 individuals8 • Around 90% of FSHD patients, symptoms usually begin before age 20, with weakness and atrophy of the muscles around the eyes and mouth, shoulders, abdominal muscles, upper arms, and lower legs, usually with asymmetric involvement. • Adult-onset and infantile-onset forms. The adult-onset is far more common • FSHD usually progresses very slowly and rarely affects the heart or respiratory system. Most people with the disease have a normal life span. However, disease severity is highly variable. • The most probable cause of FSHD is a genetic flaw (mutation) that leads to inappropriate expression of the double homeobox protein 4 gene (DUX4) on chromosome 4, in the 4q35 region7
22. Diagnosis • Chronic elevation of serum CPK level is a general indication of muscle disease. ( level does not correlate with severity of diseases) • Three serum tests showing elevated CPK levels obtained 1 month apart is diagnostic for muscular dystrophy • EMG is supportive but may be difficult to perform in children • Muscle biopsy followed by immunostaining or western blot analysis for dystrophin is recommended for diagnostic testing ---- GOLD standard • PCR tests are also available -- (may become gold standard)
23. Clinical Findings • Waddling gait • Frequent falling • Difficulty climbing stairs • Grower maneuver – describes raising from sitting to standing with the help of both arms • Weakness in shoulder girdle and trunk erectors my lead to thoracolumbar scoliosis • Pseudohypertrophy of calves (60%) • Macroglossia (30%) • Intellectual impairment The earlier the onset the more rapid the disease course Intellectual impairment – was thought to be related to limitation of education opportunity, - but equalization of education and psychometric studies showed that this was not the case. This implies a possible effect of dysfunctional dystrophin In the brain.
24. Cardiac involvement • Cardiac involvement starts early in the course of the disease though clinical signs are not usually obvious in early stages • Cardiac degeneration occurs due to replacement of myocardium by connective tissue or fat leading to dilated cardiomyopathy • No correlation has been established between severity of cardiac disses and the severity of skeletal disease • In DMD – posterobasal and contiguous lateral left ventricle walls are initial and primary sites myocardial dystrophy, in the absence of small vessel coronary artery disease in these areas • Subclinical or clinical cardiac involvement is present in about 90% of DMD/BMD patients • Cause of death in only 20% of DMD and 50% of BMD
25. • sinus tachycardia, • tall R waves in the right precordial leads, • prominent left precordial Q waves • increase QT dispersion • inverted T waves due to scaring of the posterobasal portion of the left ventricle Echocardiogram • 10%-25% will demonstrate MVP • Posterobasal hypokinesis in a thin walled ventricle and a slow relaxation phase with normal contraction is seen in DMD Initial manifestations on ECG
26. Pulmonary involvement • Pulmonary insufficiency is the leading cause of morbidity and mortality in DMD 3 • Expiration muscle function are affected first due to early onset of abdominal muscle weakness • VC increases in first decade of life and drastically decreases as diaphragmatic weakness progresses, along with IRV and TLC 2 • Scoliosis further impairs pulmonary function • For each 10 degrees of thoracic scoliosis curvature, FRC decreases by 4% 1 • 90% of patients develop a greater than 20%-degree curvature 3-4 years post being wheelchair bound
27. Anesthetic Considerations • Procedures you may encounter for patients with DMD/BMD commonly include muscle biopsies, correction of scoliosis, release of contractures, exploratory laparotomies for ileus, dental, and OB As the natural course of disease progresses the risk of surgery increases, with increased comorbid conditions associated with the later phase of the disease • Perioperative complication are not proportional to the severity of the disease and can even occur in mildly affected pts • Pts should undergo careful preoperative consultation and evaluation
28. Preoperative evaluation is KEY • Extensive history with appropriate consults • Physical exam should focus on cardiopulmonary system • Assess muscle strength • Evaluate lung mechanics is possible (ie: place face mask and see on spirometer ,NIF, Vc, TC, RR, etc • Symptoms… palpitations, dyspnea, chest pain, syncope, orthopnea, edema, aspiration, pneumonia • ECG, PFTs, and echocardiogram • Full laboratory panel • Body habitus and abnormal anatomy
29. Anesthetic Considerations • Pts may have decreased laryngeal reflexes and a prolonged gastric emptying time increasing the risk of aspiration5 • Decreased ability to cough of accumulated oral secretions predisposes MD pts to post operative respiratory tract infections • Masseter spasm is at increased risk in these patients 4 • Preparedness for a difficult airway is necessary
30. Succinylcholine / Muscular Dystrophy • Succinylcholine administration in patients with DMD and BMD is associated with life-threatening rhabdomyolysis and hyperkalemia. • There are two general mechanisms underlying succinylcholine-induced hyperkalemia: • 1) excess potassium release as a result of upregulation of abnormal extrajunctional acetylcholine receptors (i.e. burns, denervation, atrophy) • 2) development of hyperkalemia as a result of rhabdomyolysis that occurs in patients with myopathic disease states, such as DMD and BMD. • The pathophysiology of inhaled anesthetic-induced rhabdomyolysis in patients with DMD and BMD is unknown; it has been hypothesized that inhaled anesthetics exacerbate a breakdown of the muscle membranes in these patients. 6
31. MD and MH ? • Reports have suggested a relationship between DMD/BMD and malignant hyperthermia, but this association is not based on good rational grounds • Risk for MH mutation in DMD/BMD is similar to that of the general population • Incidence: 0.002 in DMD and 0.00036 in BMD Brandom B, apuyta J: epidemiology challenge in malignant hyperthermia, • The clinical event may resemble MH in many ways but is not considered “true” MH. https://ghr.nlm.nih.gov/condition/malignant-hyperthermia#genes
32. Preparing the Anesthesia Machine for MH/MD Patients9,10,11 • Ensure that anesthetic vaporizers are disabled by removing, or taping in the “OFF” position. • Most vaporizers have a significant reservoir of anesthetic agent that cannot be drained, thus draining is not an acceptable choice. • During preparation of the machine, attach a new breathing circuit and reservoir bag to the Y-piece of the circle system and set the ventilator to inflate the bag periodically. • For newer anesthesia workstations, this may require flowing 10 L/min of fresh gas for up to 104 minutes. For older machines, flow 10 L/min of fresh gas for 20 minutes. • Changing the CO2 absorbent is recommended. • Consult the manufacturer of the machine for specific instructions on preparation of the machine for an MH patient. • For both new and older machines, adding commercially available activated charcoal filters (Vapor-Clean™, Dynasthetics, Salt Lake City, UT) to the circuit will remove anesthetic gases and obviate the need for purging the system as described. However, the anesthesia machine will still need to be flushed with high fresh gas flows (≥ 10 L/min) for 90 seconds prior to placing the activated charcoal filters on both the inspiratory and expiratory ports. These filters are effective in keeping gas concentration below 5 ppm for up to 12 hours with fresh gas flows of at least 3 L/min. Also secure all succinylcholine and/or remove from room to "flush" all machines, place additional breathing bag on elbow, if the machines uses the manual breathing bag as part of the circuit (DRGER machines) set vent for example at 600 x 15 x 5 peep with high fresh flow of gases and let it run: in machines where the breathing circuit is separated from manual breathing (GE), do manual flush and on vent (2 separate flushing)
33. Emergency Treatment for An Acute MH Event • Notify surgeon to halt the procedure ASAP: Discontinue volatile agents and succinylcholine. • – If surgery must be continued, maintain general anesthesia with IV non-triggering anesthetics (e.g., IV sedatives, narcotics, amnestics and non-depolarizing neuromuscular blockers as needed) • Get dantrolene/MH cart. (Call 911 if surgicenter) • – Call for help within your institution; also, call the MHAUS Hotline (1-800-644-9737) for additional advice. (Outside the US, please call: 001-209-417-3722) • Hyperventilate with 100% oxygen at flows of 10L/min to flush volatile anesthetics and lower ETCO2. If available, insert activated charcoal filters into the inspiratory and expiratory limbs of the breathing circuit. The Vapor-Clean™ filter may become saturated after one hour; therefore, a replacement set of filters should be substituted after each hour of use. • Give IV dantrolene 2.5 mg/kg rapidly through large-bore IV, • Repeat as frequently as needed until the patient responds with a decrease in ETCO2 , decreased muscle rigidity, and/or lowered heart rate. Large doses (>10mg/kg) may be required for patients with persistent contractures or rigidity. DANTRIUM®/REVONTO® – Each 20 mg vial should be reconstituted by adding 60 ml of sterile water for injection, USP (without a bacteriostatic agent) and the vial shaken until the solution is clear. RYANODEX®– Each 250 mg vial should be reconstituted with 5 ml of sterile water for injection, USP (without a bacteriostatic agent) and shaken to ensure an orange-colored uniform, opaque suspension. • If giving large doses (> 10 mg/kg) without symptom resolution, consider alternative diagnoses. • Obtain blood gas (venous or arterial) to determine degree of metabolic acidosis. • Cool the patient if core temperature is >39°C or less if rapidly rising. Stop cooling when the temperature has decreased to <38°C. • If hyperkalemia (K > 5.9 or less with ECG changes) is present, treat with: -Calcium chloride 10 mg/kg (maximum dose 2,000 mg) or calcium gluconate 30 mg/kg (maximum dose 3,000 mg) for life-threatening hyperkalemia • Sodium bicarbonate. – 1-2 mEq/kg IV (maximum dose 50 mEq) • Glucose/insulin • – For pediatric patients: 0.1 units regular insulin/kg IV and 0.5 grams/kg dextrose (% in formulation not important) • – For adult patients: 10 units regular insulin IV and 50 ml 50% dextrose • – Check glucose levels hourly • For refractory hyperkalemia, consider albuterol (or other beta-agonist), kayexelate, dialysis, or ECMO if patient is in cardiac arrest. • Treat dysrhythmias with standard medication but avoid calcium channel blockers. • Diurese to >1ml/kg/hr urine output. If CK or K+ rise, assume myoglobinuria and give bicarbonate infusion of 1 mEq/kg/hr, to alkalinize urine • Institute appropriate monitoring including: core temperature, urine output with bladder catheter, and consider arterial and/or central venous monitoring if warranted by the clinical severity of the patient. • Follow: HR, core temperature, ETCO2 , minute ventilation, blood gases, K+, CK, urine myoglobin and coagulation studies as warranted by the clinical severity of the patient. • When stable, transfer to post anesthesia care unit or intensive care unit for at least 24 hours. Key indicators of stability include: https://www.mhaus.org/healthcare- professionals/managing-a-crisis/ -ETCO2 is declining or normal -Heart rate is stable or decreasing with no signs of ominous dysrhythmias -Hyperthermia is resolving -If present, generalized muscular rigidity has resolved Notify surgeon to halt the procedure ASAP: Discontinue volatile agents and succinylcholine. Hyperventilate with 100% oxygen Give IV dantrolene 2.5 mg/kg rapidly through large-bore IV Cool the patient if core temperature is >39°C Obtain blood gas
34. References 1. Hoffman E: Dystrophin: the protein product od Duchenne muscular dystrophy locus. Cell 51:919-928, 1987 2. Hahn A, Bach JR, Delaubier A, et al: Clinical implications of maximal respiratory pressure determinants for individuals with Duchenne muscular dystrophy. Arch Phys Med Rehabil 78L 1:6, 1997 3. Morris P: Duchenne muscular dystrophy : A challenge for anaesthetist. Paediatr Anaesth 7: 1-4, 1997 4. Breucking E, Reimnitz P, Schara U, Mortier W. [Anesthetic complications. The incidence of severe anesthetic complications in patients and families with progressive muscular dystrophy of the Duchenne and Becker types]. Anaesthesist. 2000;49(3):187-195. doi:10.1007/s001010050813 5. Stevens, R. D: Neuromuscular disorders and anesthesia. Current Opinion in Anaesthesiology, 12:693-698, 2001 6. Segura, L.G., Lorenz, J.D., Weingarten, T.N., Scavonetto, F., Bojanic, K., Selcen, D., and Sprung, J. (2013). Anesthesia and Duchenne or Becker muscular dystrophy: Review of 117 anesthetic exposures. Pediatric Anesthesia, 23, 855–864. 7. Gabriëls, J. et al. Nucleotide sequence of the partially deleted D4Z4 locus in a patient with FSHD identifies a putative gene within each 3.3 kb element. Gene (1999). doi:10.1016/S0378-1119(99)00267-X 8. Deenen, J. C. W. et al. EPopulation-based incidence and prevalence of facioscapulohumeral dystrophy. Neurology (2014). doi:10.1212/WNL.0000000000000797 9. Shanahan H, O’Donoghue R, O’Kelly P, Synnott A, O’Rourke J. Preparation of the Drager Fabius CE and Drager Zeus anaesthetic machines for patients susceptible to malignant hyperthermia. Eur J Anaesthesiol. 2012;29 (5): 229-34. 10. Jones C, Bennett K, Kim T, Bulger T, Pollock N. Preparation of Datex-Ohmeda Aestiva and Aisys anaesthetic machines for use in malignant hyperthermia susceptible patients. Anaesth Intensive Care. 2012;40 (3): 490-7. 11. Kim TW, Nemergut ME. Preparation of modern anesthesia workstations for malignant hyperthermia-susceptible patients: a review of past and present practice. Anesthesiology. 2011: 114(1): 205-12.
35. Neuroleptic Malignant Syndrome (NMS) • Rare, potentially fatal condition due to antipsychotic drug therapy • May reflect dopamine depletion in the CNS • Can occur anytime during the course of antipsychotic treatment but often is manifest during the first few weeks of therapy or following an ↑ in drug dosage. • Clinical manifestations usually develop over 24-72 hours F ever E ncephalopathy V ital signs unstable E levated labs R igidity (vs myoclonus in serotonin syndrome) S weating
36. Management •Resuscitation & ICU monitoring following trigger •Stop offending agents •Supportive treatment: cooling, treat acidosis/electrolyte abnormalities, hemodynamic support •Pharmacologic (case reports, no strong evidence): • Bromocriptine: PO/NG 2.5 mg q8-12 hrs • Dantrolene: IV 2.5mg/kg bolus, up to 10mg/kg/day • Amantadine: initial dose is 100 mg PO/NG & titrated upward as needed to a maximum dose of 200 mg q12h • Benzodiazepines •Rule out other high risk conditions on differential diagnosis •"Trigger free” anesthetic in patients with history of NMS (controversial)