Anesthesia and Uncommon Disorders

1. Anesthesia and Uncommon Disorders Sarah Kennedy March 27, 2009

2. Outline Malignant Hyperthermia Endocrine Pheochromocytoma Auto immune disorders Rheumatoid Arthritis Lupus Guillian Barre Multiple Sclerosis Amyotrophic Lateral Sclerosis Substance Abuse

3. Malignant Hyperthermia An uncommon, life-threatening, hypermetabolic disorder of skeletal muscle triggered in susceptible individuals by potent inhalation agents and succinylcholine

4. Malignant Hyperthermia Uncontrolled increase in intracellular calcium in skeletal muscle Ryanodyne receptor fails in the sarcoplasmic reticulum leading to decreased Ca reuptake from within the cell causing a 500-fold increase in intracellular Ca Sustained intense muscle contraction Glycolysis Heat production

5. Malignant Hyperthermia Triggers Succinylcholine Inhalational agents: halothane, isoflurane, sevoflurane, desflurane, enflurane Stress, muscle trauma, exercise Prior uneventful general anesthetic does not rule out the possibility of MH Prior uneventful general anesthetic does not rule out the possibility of MH

6. Malignant Hyperthermia PMH Strabismus, myalgias on exercise Tendency to fever Myoglobinuria Muscular disease Intolerance to caffeine Elevated CPK Gold standard preop test = muscle biopsy with halothane-caffeine contracture test – 85% specific, and 100% sensitive – caffeine causes muscle to contract and halothane in the MH pt causes more forceful contraction Central-core disease Duchenne’s muscular dystrophy King-Denborough syndrome Osteogenesis imperfecta Myotonia Fukuyama’s muscular dystrophy Becker’s muscular dystrophy Gold standard preop test = muscle biopsy with halothane-caffeine contracture test – 85% specific, and 100% sensitive – caffeine causes muscle to contract and halothane in the MH pt causes more forceful contraction Central-core disease Duchenne’s muscular dystrophy King-Denborough syndrome Osteogenesis imperfecta Myotonia Fukuyama’s muscular dystrophy Becker’s muscular dystrophy

7. Malignant Hyperthermia Unexplained tachycardia Most sensitive sign – unanticipated increase in EtCO2 Decrease in SaO2 & SpO2 Muscle rigidity Dysrhythmias Tachypnea Cyanosis and mottling of skin Sweating Labile BP Trismus (masseter spasm) after succinylcholine Darkening of blood in surgical field Decreased mixed venous saturation Cola-colored urine (myoglobinuria) Heating and exhaustion of CO2 absorber Hyperthermia – late but confirming sign Labs mirror muscle breakdown: Myoglobinuria Increased K+ > 6meq/L and CK >10,000 IU/L Initial metabolic acidosis, then a combined metabolic & respiratory acidosis Late complications: Cerebral edema Myoglobinuric renal failure Consumptive coagulopathy Hepatic dysfunction Pulmonary edema

8. Malignant Hyperthermia Treatment Stop all triggering agents CALL FOR HELP 1-800-MH-HYPER Alert surgeon and stop the surgery! Hyperventilate with 100% O2 at high flows Dantrolene 2.5 mg/Kg IV ASAP then Q5min. until symptoms controlled or up to 10 mg/Kg total Sodium bicarbonate 1-2 meq/Kg IV Cooling measures Iced IV solutions Cold body cavity lavage Cooling blanket Ice bags

9. Malignant Hyperthermia Treatment Treat hyperkalemia with dextrose 25-50g & regular insulin 10-20 units IV Inotropes and antiarrhythmic agents PRN Change circuit and soda lime Promote urine output, maintain >2cc/Kg/hr with IVF’s, Art line, CVP Procainamide Lasix 0.5-1 mg/Kg IV, Mannitol 1 g/Kg IV Procainamide Lasix 0.5-1 mg/Kg IV, Mannitol 1 g/Kg IV

10. Malignant Hyperthermia Treatment Labs ICU for 24-48 hrs Continue dantrolene 1 mg/Kg IV Q6hrs for 72 hrs to prevent a recurrence Avoid calcium channel blockers secondary to hyperkalemia and myocardial depression Labs (6, 12, 24 hrs after episode): ABG, K, Ca, BUN/Cr, lactate, urine myoglobin, urine output, CPK, PT, INR, PTT, platelets, EtCO2, mixed venous saturation, core body temp. Labs (6, 12, 24 hrs after episode): ABG, K, Ca, BUN/Cr, lactate, urine myoglobin, urine output, CPK, PT, INR, PTT, platelets, EtCO2, mixed venous saturation, core body temp.

11. Malignant Hyperthermia Late Complications Renal failure Coagulopathies Pulmonary edema Cerebral edema Hepatic failure Left heart failure DIC Skeletal muscle swelling Rhabdomyolysis Death

12. Malignant Hyperthermia Safe Drugs Benzodiazepines Barbiturates Etomidate Narcotics Local anesthetics Propofol Nondepolarizing muscle relaxants N2O Ketamine Use ketamine & pancuronium with caution because the tachycardia may mask early MH

13. Pheochromocytoma Catecholamine-secreting tumor that originates in the adrenal medulla or in the chromaffin tissues along the paravertebral sympathetic chain, extending from the pelvis to the base of the skull Age: 30-50 years 50% deaths occur during unrelated surgery or pregnancy Diagnosis by 24 hour urine for norepinepherine and CT scan Associated with Multiple endocrine neoplasia (MEN) Multiple endocrine neoplasia type 2a or 2b Inherited autosomal traitMultiple endocrine neoplasia type 2a or 2b Inherited autosomal trait

14. Pheochromocytoma Clinical Manifestations: Tachycardia Diaphoresis Headache Hypertension – most common symptom Hyperglycemia Hypovolemia Tremulousness Palpitations Weight loss Treatment is surgical excision of the tumor(s) Hypeglycemia secondary to alpha adrenergic inhibition of insulinHypeglycemia secondary to alpha adrenergic inhibition of insulin

15. Pheochromocytoma Anesthetic Management Correct hypovolemia (serial hematocrits) Alpha blockade before beta blockade Alpha blockage: phenoxybenzamine 10-20 mg PO bid for 14 days pre-op Pre-op propranolol 40 mg PO benzos with scopalamine Avoid histamine releasing drugs Lines Arterial line, CVP, +/- PA Alpha blockade: phenoxybenzamine drug of choice. It is a noncompetitive presynaptic a2 and postsynaptic a1 adrenergic antagonist of long duration 24-48 hrs Beta blockage for control of tachycardia, hypertension, catecholamine induced supraventricular arrhythmias If you beta block first, the heart may be depressed to the point that CO suffers secondary to unopposed alpha mediated vasoconstrictionAlpha blockade: phenoxybenzamine drug of choice. It is a noncompetitive presynaptic a2 and postsynaptic a1 adrenergic antagonist of long duration 24-48 hrs Beta blockage for control of tachycardia, hypertension, catecholamine induced supraventricular arrhythmias If you beta block first, the heart may be depressed to the point that CO suffers secondary to unopposed alpha mediated vasoconstriction

16. Pheochromocytoma Induction barbituates, benzos or propofol fentanyl or sufentanil suxx questionable, no pancuronium Lidocaine 1-2 mg/kg Maintenance sevoflurane or isoflurane Fentanyl Treat hypertension with phentolamine 1-5 mg IV or nitroprusside Treat reflex tachycardia with an esmolol infusion Sevo and iso provide cardiac stability plus you can rapidly change anesthetic depth. No des b/c of tachycardia Esmolol bc of short half lifeSevo and iso provide cardiac stability plus you can rapidly change anesthetic depth. No des b/c of tachycardia Esmolol bc of short half life

17. Pheochromocytoma Critical Times Intubation Surgical manipulation of tumor After ligation of tumor’s venous drainage

18. Rheumatoid Arthritis Chronic, inflammatory, autoimmune disorder Affects synovial membranes with systemic involvement of peripheral joints and sometimes other organs Cause Unknown Rheumatoid factor (an antiimmunoglobulin antibody) present in 80% of patients with RA Onset Ages 30-50 Affects women more than men This antibody solicits an inflammatory cascade that damages synovial and joint tissue. This antibody solicits an inflammatory cascade that damages synovial and joint tissue.

19. Rheumatoid Arthritis Peripheral joints Hands, feet, wrist Pain, inflammation, erosion of bone Nonarticular muscular structures Tendons, ligaments, and fascia Systemic Involvement Cardiovascular Pericardial thickening and effusion Myocarditis Conduction defects LV failure (CHF), valve fibrosis, arteritis involving coronary arteries, myocardial infarction Aortitis causing dilation of aortic root leading to regurg It is considered “polyarticular”; that is it affects many joints. Can also affect knees, shoulder…larger jointsIt is considered “polyarticular”; that is it affects many joints. Can also affect knees, shoulder…larger joints

20. Rheumatoid Arthritis Systemic Involvement Lungs Pleural effusion Nodules in pulmonary tissue Interstitial pulmonary fibrosis Restrictive pulmonary changes with decreased lung volumes and vital capacity Leads to V/Q mismatch decreasing arterial oxygenation Neuromuscular Carpal tunnel syndrome Cervical nerve root compression Weakness of muscles adjacent to diseased joint Neuropathy resulting from nerve compression Blood Anemia secondary to hemodilution or ASA therapy Thrombocytopenia Skin Thin and atrophic skin secondary to disease and immunosupressive drugs

21. Rheumatoid Arthritis Joint Involvement Tempromandibular joint Limitations in mandibular motion Thoracic, lumbar, sacral spine usually spared Cervical spine involvement is frequent and extensive Atlantoaxial subluxation (partial or complete dislocation of the 1st and 2nd cervical vertebrae) Cricoarytenoid arthritis Edema of the arytenoids, upper airway obstruction Joints of the larynx Limitations of the vocal cord movement, edema Morning stiffness is a hallmark of RA. TMJ may lead to limitation of the mandibular motionMorning stiffness is a hallmark of RA. TMJ may lead to limitation of the mandibular motion

22. Rheumatoid Arthritis Anesthesia Management Baseline ABGs, PFTs, clotting times, CBC, ECHO/Stress Test Assess airway Temporomandibular joint Cricoarytenoid joints Cervical spine ROM Assess steroid use Possible awake FOI, glidescope Proper positioning Careful airway management/ventilation TMJ may not allow for full opening of the mouth Possible pulmonary issues, and anemia Long term NSAIDs can may result in platelet dysfunction Corticosterioid use may cause HPA suppression requiring stress dose steroid need Generalized bone demineralization may increase risk of fractures when positioning. Hoarseness may indicate cricoarytenoid joint involvement, thus requiring smaller ET tube (because of smaller glottic opening)TMJ may not allow for full opening of the mouth Possible pulmonary issues, and anemia Long term NSAIDs can may result in platelet dysfunction Corticosterioid use may cause HPA suppression requiring stress dose steroid need Generalized bone demineralization may increase risk of fractures when positioning. Hoarseness may indicate cricoarytenoid joint involvement, thus requiring smaller ET tube (because of smaller glottic opening)

23. Systemic Lupus Erythematous Chronic, multi-system autoimmune disease affecting joints, tissue, systemic organs and the central nervous system About 1.5 million Americans have SLE Affects women 9 times more likely than men Can occur at any age Higher incident in African-American women

24. Systemic Lupus Erythematous Causes Lack of supression of B lymphocytes by T- lymphocytes such that antibodies are produced against host antigens Triggers Genetic predisposition Environmental triggers Drug reactions Reactions against procainimide, hydralazine, sulfonamides, and some non barbituate anticonvulants (precipitate exacerbations) Reactions against procainimide, hydralazine, sulfonamides, and some non barbituate anticonvulants (precipitate exacerbations)

25. Systemic Lupus Erythematous Articular Manifestations Systemic Arthritis Hands Wrists Elbows Knees Ankles Avascular necrosis Femoral head or condyle

26. Systemic Lupus Erythematous Systemic Manifestations Heart Pericarditis Tachycardia CHF LV dysfunction Noninfectious endocarditis involving mitral and aortic valves Lungs Lupus pneumonia Pulmonary infiltrates, pleural effusion, dry cough, dyspnea, arterial hypoxemia Presents as restrictive lung disease CNS Cognitive changes, mood disturbances, schizophrenia, deterioration of intellectual capacity Systemic Manifestations Renal Glomerulonephritis with proteinuria resulting in hypoalbuminemia Liver Hepatitis in severe cases Neuromuscular Loss of strength in muscle adjacent to joints Neuropathy resulting from nerve compression Skin Malar or “butterfly” rash is presenting sign in 50% of patients Rash on trunk (red scaly patches), alopecia Photosensitivity

27. Systemic Lupus Erythematous

28. Systemic Lupus Erythematous Anesthesia Management Baseline ABGs, PFTs, clotting times, CBC, ECHO/Stress Test Pain/Stress management (assess steroid use) Airway assessment Proper positioning/Peripheral neuropathy Careful muscle relaxant titration Fluid management Avoid procainimide, hydralazine, sulfonamides, and many anti-seizure agents (precipitates exacerbations).

29. Guillain Barre Autoimmune disorder that attacks the myelin sheath of the peripheral nervous system Sudden onset of ascending motor paralysis, areflexia, and variable paresthesias Symptoms can increase in intensity until the muscles cannot be used at all and the patient is almost totally paralyzed Occurrence/Triggers Viral, respiratory and gastrointestinal infections S/P surgery or vaccinations Paraneoplastic syndrome associated with Hodgkin’s Complication of HIV Also known ass acute idiopathic polyneuritis Difficulty swallowing, impaired respiration d/t intercostal muscle paralysis are most serious symptoms Pain in the form of backache, headache, tenderness of skeletal muscles to deep pressureAlso known ass acute idiopathic polyneuritis Difficulty swallowing, impaired respiration d/t intercostal muscle paralysis are most serious symptoms Pain in the form of backache, headache, tenderness of skeletal muscles to deep pressure

30. Guillain Barre Anesthetic Considerations Manage respiratory complications Autonomic Nervous System instability Closely monitor for fluctuations in BP, tachycardia, conduction defects Exaggerated hypertension during laryngoscopy, incision, extubation Avoid suxx secondary to risk of hyperkalemia Regional anesthesia controversial but generally not recommended Profound hypotension in response to changes in posture, blood loss, or positive airway pressureProfound hypotension in response to changes in posture, blood loss, or positive airway pressure

31. Guillain Barre Treatment: No known cure Goal is to treat symptoms and complications Plasma exchange/plasmapheresis High dose immunoglobin therapy Prognosis Most patients recover completely 10% die from complications 10% long term neurologic problems

32. Multiple Sclerosis Etiology unknown Multifactorial Viral, genetic factors Immunologically mediated destruction of myelin occuring randomly in the corticospinal tract neurons of the brain and spinal cord, slowing conduction Signs/symptoms visual and gait disturbances limb paresthesias and weakness urinary incontinence Onset: age 15 - 40 years, females: males 2:1 Characterized by symptomatic exacerbations and remissions Exacerbations due to stress, fatigue, infections, hyperthermia, surgery, trauma

33. Multiple Sclerosis Anesthetic Considerations Avoid Elective surgery during relapses Regional anesthesia controversial Avoid hyperthermia Succinylcholine is best avoided d/t a potential hyperkalemic response. Lower doses of nondepolarizing relaxants should be used in patients w/ baseline motor weakness—shorter duration nondepolarizing relaxants may be best in this situation. It is thought that elevated temperatures cause complete blocking of conduction in demyelinated neurons. Even modest increases in body temperature (>1°C) must be avoided. REGIONAL may be beneficial for the MS patient due to decreased stress response of surgery. some studies show spinal anesthesia to exacerbate symptoms It is thought that elevated temperatures cause complete blocking of conduction in demyelinated neurons. Even modest increases in body temperature (>1°C) must be avoided. REGIONAL may be beneficial for the MS patient due to decreased stress response of surgery. some studies show spinal anesthesia to exacerbate symptoms

34. Amyotrophic Lateral Sclerosis Lou Gehrig’s disease Terminal Progressive diffuse degeneration of upper and lower motor neurons Amyotrophic means “without muscle nutrition” or “progressive muscle wasting” and refers to the lower motor neuron components of this syndrome. Lateral sclerosis refers to scarring of the corticospinal tract in the lateral column of the spinal cord, and is the upper motor neuron component of this syndrome. Typically ALS is seen as early as 20 years of age; however, most commonly around age 60. At a younger age ALS occurs predominantly in males, but as the age progresses the occurrence in gender equals out. A family history is seen in 5-10 percent of patents. ALS is rare and seen only 1 in 100,000 persons. Amyotrophic means “without muscle nutrition” or “progressive muscle wasting” and refers to the lower motor neuron components of this syndrome. Lateral sclerosis refers to scarring of the corticospinal tract in the lateral column of the spinal cord, and is the upper motor neuron component of this syndrome. Typically ALS is seen as early as 20 years of age; however, most commonly around age 60. At a younger age ALS occurs predominantly in males, but as the age progresses the occurrence in gender equals out. A family history is seen in 5-10 percent of patents. ALS is rare and seen only 1 in 100,000 persons.

35. Amyotrophic Lateral Sclerosis Reduction and degeneration of large motor neurons in the spinal cord, brainstem, and cerebral cortex pre-motor and motor areas Cranial nerves III, IV and VI not involved Lower motor neuron degeneration causes denervation of motor units Viable lower motor neurons attempt to compensate via: Distal intramuscular sprouting Reinervation Enlargement of motor units Death of motor neurons results in axonal degeneration and secondary demyelination with glial proliferation and sclerosis, causing scarring. Death of motor neurons results in axonal degeneration and secondary demyelination with glial proliferation and sclerosis, causing scarring.

36. Amyotrophic Lateral Sclerosis Regeneration of achetylcholine receptors Muscle weakness and atrophy Loss of ambulation Oropharyngeal dysfunction Weight loss Respiratory failure Spasticity of limb and bulbar muscles Pseudobulbar affect - pathologic uncontrollable crying or laughing in 50% of patients Regeneration of achetylcholine receptors is an attempt for the body to reach out to a nerve cell that is no longer there. The degeneration of the motor neurons causes symptomsRegeneration of achetylcholine receptors is an attempt for the body to reach out to a nerve cell that is no longer there. The degeneration of the motor neurons causes symptoms

37. Amyotrophic Lateral Sclerosis First Signs Unexplained upper or lower extremity weakness Difficulty speaking or swallowing Generalized muscle twitching The rate of progression is completely individualized. Diagnosing ALS can be done by neurological physical exam and patient history. A follow up confirmation of diagnosis is recommended with an EMG and nerve conduction test. The rate of progression is completely individualized. Diagnosing ALS can be done by neurological physical exam and patient history. A follow up confirmation of diagnosis is recommended with an EMG and nerve conduction test.

38. Amyotrophic Lateral Sclerosis Anesthetic Considerations Increased risk of MH NO SUXX Causes a massive shift of intracellular potassium to be released Serum potassium levels can be fatal Increased saliva production glycopyrrolate (Robinul) benzotropine (Cogentin) trihexyphenidyl hydrochloride (Artane) transdermal hyoscine (Scopolamine) Dysphagia Full stomach precautions Hypothermia Fragile muscles Proper positioning, padding, use of tourniquet Patients with ALS have an abnormally high amount of acetylcholine receptors that are not being used related to the regeneration of receptors in response to motor neuron degeneration. When these patients are given succinylcholine for induction the succinylcholine binds to vast acetylcholine receptors and causes a massive shift of intracellular potassium to be released. Hypothermia secondary to loss of autonomic functionPatients with ALS have an abnormally high amount of acetylcholine receptors that are not being used related to the regeneration of receptors in response to motor neuron degeneration. When these patients are given succinylcholine for induction the succinylcholine binds to vast acetylcholine receptors and causes a massive shift of intracellular potassium to be released. Hypothermia secondary to loss of autonomic function

39. Substance Abuse Socially acceptable drugs Alcohol Nicotine Medically prescribed drugs Valium Xanax Opiods Illegal substances Cocaine Marijuana Ecstasy Physical dependence most often seen with opiods, barbiturates, alcohol and benzos Barbiturate withdrawal most lethal and dangerous of withdrawal syndromes

40. Substance Abuse Obtain thorough history, use suspicion Hard IV stick? Look at arms, veins Skin infections, thrombophlebitis, malnutrition, endocarditis, Hep B and C, HIV Acute Chronic Cancel elective surgery Withdrawal symptoms Admits to use Necessary surgery Perioperative doses of abused substance should be substituted Opiates for any opiate Aviod opiods with mixed agonist-antagonist activity because they can precipitate withdrawal Benzos for alcohol Post op withdrawal control Clonidine Consider regional Different requirement for acute and chronic substance abuseDifferent requirement for acute and chronic substance abuse