Ofer M. Wellisch 1/6 1/23/11A 40-year old 50 kg woman with well-controlled myasthenia gravis is scheduled for aradical hysterectomy for cancer. She has completed a course of chemotherapy andradiation therapy. She is currently on Mestinin (pyridostigmine) 60 mg qid. Bloodpressure is 105/95 mmHg, pulse is 96 bpm, and hematocrit is 30 gm/dl. Preoperative evaluationI. Evaluation of myasthenia1. What is the etiology of myasthenia? - Weakness associated with myasthenia is thought to be due to autoimmune destruction or inactivation of postsynaptic acetylecholine receptors at the NMJ, leading to a reduced number of receptors and loss of folds in the postsynaptic membranes. - IgG against nicotinic acetylcholine receptors in NMJ found in 85-90% of pts with generalized myasthenia gravis and 50-70% with ocular myasthenia. - 10-15% develop thymoma, whereas develop 65% thymic hyperplasia - 10% of pts develop other AI disorders such as hypo/hyperthyroidism, and rheumatoid arthritis.2. What is the treatment for myasthenia? - Treatment is largely symptomatic. Anticholinesterase agents such as pyridostigmine are used to increase neurotransmission at the neuromuscular junction. Corticosteroids and immunotherapy with azathioprine might produce long-term improvement. Plasmapheresis might be effective by eliminating the circulating antibody. Finally, many myasthenic patients have an associated thymoma, and surgical removal of the thymus may be indicated.3. How does pyridostigmine work? - Neostigmine, edrophonium, and pyridostigmine inhibit acetylcholinesterase. This inhibition is present at all cholinergic synapses in the peripheral nervous system. Thus, the anticholinesterases have potent parasympathomimetic activity, which is attenuated or abolished by the administration of an antimuscarinic agent, atropine or glycopyrrolate. - Effective duration of pyridostigmine is 2-4 hrs.4. What is the difference between pyridostigmine and physostigmine?
Ofer M. Wellisch 2/6 1/23/11 - Neostigmine, edrophonium, and pyridostigmine are quaternary ammonium compounds, which do not penetrate the blood–brain barrier well. - Physostigmine is a tertiary amine and can thus cross the blood–brain barrier. For this reason, in addition to myasthenia gravis, it is has also been used to treat glaucoma, Alzheimers disease and delayed gastric emptying, as well as to treat the CNS effects of atropine, scopolamine and other anticholinergic drug overdoses.5. What are signs of cholinergic crisis? - Cholinergic crisis is characterized by increased weakness and excessive muscarinic effects such as salivation, diarrhea, miosis, and bradycardia. - Cholineric crisis may be precipitated by administration of anticholinestrase. - Edrophonium test will differentiate between myasthenic and cholinergic crisis. 10 mg edrophonium IV resulting in increased weakness points to cholinergic crisis, whereas a brief increase in strength is indicative of myasthenia. The “tensilon test” is thus also used to diagnose myasthenia.6. What is the management? - Anticholinergics are used alone to treat mild disease. - Moderate to severe disease is treated with combination of anticholinestrase and immunomodulating therapy. - First line immunomodulating therapy is corticosteroids, followed by azathioprine, cyclosporine, cyclophosphamide, mofetil, and IVIG has also been used. - Plasmaphoresis is reserved for pts with dysphagia or respiratory failure or to normalize muscle strength preoperatively.II. Assessment of respiration1. Are pulmonary function tests indicated? Why or why not? - PFTs necessary if respiratory impairement exists. - After thymectomy, the need for mechanical support of ventilation can usually be predicted from preoperative lung function tests. - Disease duration >6 yrs, concomitant pulmonary disease, peak inspiratory pressure < -25 mm H2O, VC < 4ml/kg, pyridostigmine dose >750 mg/24 hrs are predictive for postop ventilation following thymectomy. Note: Disease improvement is usually delayed, even by years, following thymectomy; still, 85% of pts under age 55 show improvement.
Ofer M. Wellisch 3/6 1/23/11 - As a side note: Preop baseline T4/T1 train of four ratio <0.9 is indicative of increased sensitivity to nondepolarizing NMBAs. Note: MG pts are insensitive to succinylcholine and require 2-3x dose.2. What are your expected findings? - This pt is said to have well-controlled MG and thus should have no underlying functional respiratory deficits. This pt also takes less than 750 mg/day pyridostigmine.3. How does this influence your treatment? - Inform pt of possibility of post-op ventilation. Avoid excessive sedation/ premedication. - Did pt have previous surgeries? Was pt taken off anticholinestrase? If so, was this tolerated? It is likely pt would tolerate stopping medication preop and restart with other oral intake post op. IV (1/30 dose) may be used if necessary post op. Intraoperative courseI. Selection and management of anesthesia1. What anesthetic technique will you use? 2. What induction agents will you use? 3.How will you intubate the patient? Explain. 4. Which maintenance agent will you use?Explain your choice. 5. Are neuromuscular properties important? Explain.6. The surgeon requests deliberate hypotension. How does this affect your anestheticchoice? 7. What are the pros and cons of myocardial depression vs vasodilation? - Avoid opiods and benzodiazepines premeds - Epidural for surgical anesthesia (T6 level) and post op pain management. Slowly build up level for safe and reliable block. - Propofol induction with volatile agent by mask followed by propofol infusion-> usually provides sufficient relaxation for tracheal intubation. The oropharynx and cords may be sprayed with lidocaine prior to intubation. - Propofol and volatile agents are safe for use with MG. - I would avoid nondepolarizing NMBA and use sux 2mg/kg for intubation if absolutely necessary. If surgeon requires better neuromuscular blockade beyond neuraxial blockade, volatile agents and propofol
Ofer M. Wellisch 4/6 1/23/11 infusion, a careful titration of (start 1/3 dose) nondepolarizing agent may be used up-front; however, this may result in complete and prolonged paralysis. - If nondepolarizing NMBA used: short acting cisatracurium generally preferred. - Epidural and propofol infusion will vasodilate. Propofol will somewhat depress myocardium as would sevo or iso. Desflurane may be used to minimize myocardial depression. All volatile agents will drop SVR. - I suppose permissive myocardial depression may be preferred by surgeon vs volatile anesthetic if the primary concern is minimizing blood loss.II. Provision of relaxation (discussed above)1. Do you expect a problem with using succinylcholine in this patient? Explain.2. Can vecuronium or atracurium be used safely for relaxation? Explain.3. Is a nerve stimulator needed? Why or why not?4. What is the significance of stimulating with the stimulator?III. Management of arrhythmias1. The patient develops premature atrial contractions. What is the etiology? - Non-specific ECG abnormalities, cardiomyopathy and heart failure may occur with MG2. What is the significance? - Anticholinergics usually abolish arrythmias which are often resistant to b-blockers and amiodarone.3. Should they be treated? - Not with typical antiarrhythmics as they may exacerbate MG4. What is your treatment? - Consider neostigmine5. Atrial fibrillation occurs. What is your treatment? - Neostigmine
Ofer M. Wellisch 5/6 1/23/11IV. Evaluation of hematuria and oliguria1. For two hours postoperatively, the patient has only 50 ml of urine. What is yourdifferential diagnosis? - 0.5 ml/kg/hr seems pretty good…2. The urine sodium is 8 mEq/l, and is pink. What is your differential diagnosis? - Worry about ureteral injury3. How do you establish a diagnosis?4. What is the significance of this occurrence?5. Would you order other tests?6. What is your treatment? Postoperative courseI. Management of ventilation1. What are your criteria for extubation? - VC > 10 ml/kg, RR <30, TV > 5ml, inspiratory force > 25 cm H2O, PaO2 > 65 (FiO2 < 40%), PaCO2 < 50. Pt aware and responsive. Also T4/T1 > 0.92. Describe the rationale behind each criterion.3. Vital capacity is 400 ml with the endotracheal tube in place while the patient isspontaneously breathing. pH=7.42, paCO2=40mmHg, and paO2=100mmHg on 30%FIO2. How would you proceed? - I would wait to achieve VC > 500 ml prior to attempting extubation. Otherwise all criteria are met.II. Management of postoperative pain1. The surgeon suggests continuous epidural for pain relief. Do you agree? - Yes. Although, Ketorolac may be useful as adjunct to epidural or low dose IV morphine.
Ofer M. Wellisch 6/6 1/23/112. Describe the hazards of epidural narcotics vs local anesthetics. - Ester local anesthetics may have much longer duration due to anticholinergic treatment. Use amides3. What protocol do you use? - Amide local (ropivicaine); esters such as chloroprociane should be avoided.III. Evaluation of postoperative nerve injury1. On postoperative day one, the patient complains of numbness and weakness of theright leg. What is your differential diagnosis?2. What are the signs of obturator nerve damage? - Pain in the groin which can radiate into the middle of the thigh down to the knee, and weakness or instability of the leg.3. What are the signs of femoral nerve damage? - Quadricepts weakness -> cannot lift leg4. What are your recommendations? - Self limited injury which may have resulted from positioning intraoperatively. Should improve in time.