Effects of anesthetic agents on patients with muscle

disorders :intravenous anesthetics

Claudio Melloni

Servizio di Anestesia e Rianimazione

Ospedale di Faenza(RA)

Ist statement:

• i.v anesthetics do not cause

• rhabdomyolysis

• MH

• hyperpotassiemia

Increased sensitivity to iv drugs

• Thiopenthal(tiopentone)• myotonic dystrophy

– Bourke T, Zuck D. Thiopentone in dystrophia myotonica. Br J Anaesth 1957; 29:35-8.

– Dundee JW. Thiopentone in dystrophia myotonica. Anesth Analg 1952; 31:257-62

• hyperkalemic periodic paralysis – Egan TJ, Discavage WJ. Hyperkalemic periodic paralysis. Pediatrics 1959;

24:761-3.– , Atkinson RS, Rushman GB, Davies NJH. Lee’s synopsis of anaesthesia.

11th ed. Oxford, UK: Butterworth-Heinemann, 1993; 419-40. • 56 year male with ophthalmoplegia who required only 75 mg of

thiopentone for loss of eyelid reflex– (James RH. Thiopentone and ophthalmoplegia plus [letter]. Anaesthesia

1965; 40:88.) • Charcot-Marie-Tooth syndrome (CMT)

– Hirota K, Muraoka M, Sugihara K, et al. Anesthetic experience of Charcot-Marie-Tooth disease. Jpn J Anesth 1988; 37:207-10.

Kotani,N,Hirota K,Anzawa N,Takamura,K, Sakai T,Matsuki A..Motor and Sensory Disability Has a Strong Relationship to Induction Dose of Thiopental in Patients with the Hypertropic Variety of Charcot-Marie-Tooth Syndrome.Anesth Analg 1996; 82:182-6..

• Mean Induction dose of thiopental:• MID in the control patients: 3.7 ± 1.1 mg/kg

(mean ± SD). • The 95% confidence interval of the MID in

control normal patients : 2.5–4.9 mg/kg.

• In 11 patients (No. 1–11), an MID of 0.83–2.4 mg/kg proved to be sufficient. The remaining 9 patients (No. 12–20) required 2.5–5.0 mg/kg as the MID.

Relationship bertween minimun induction doses of thiopental and motor and sensory disability scores of 20 patients with CMT disease(Kotani,et a.Motor and Sensory Disability Has a

Strong Relationship to Induction Dose of Thiopental in Patients with the Hypertropic Variety of Charcot-Marie-Tooth Syndrome.Anesth Analg 1996; 82:182-6..

Stackhouse R, Chelmow D, Dattel BJ: Anesthetic complications in a pregnant patient with nemaline

myopathy. Anesth Analg 79:1195, 1994• GA for C/S• the patient received sodium citrate (30 mL per os), was preoxygenated for 4 min, and had

a modified rapid-sequence induction of anesthesia performed using thiopental (320 mg: 4 mg/kg) and vecuronium (10 mg) while applying cricoid pressure. The patient was ventilated with isoflurane (1%) in oxygen until twitch response was eliminated (4 min postinduction).

• The first attempt at laryngoscopy with a Mac 3 blade failed. A second laryngoscopy with a Miller 2 blade was unsuccessful because it was not long enough to lift the epiglottis. Ventilation was reinstituted after rapid oxygen desaturation from 98% to 80%, and it continued until oxygen saturation returned to 95%. Copious oral secretions were suctioned. Laryngoscopy(3) with a Mac 4 blade was performed twice and provided visualization only of the arytenoids. Nonetheless, the endotracheal tube was passed anterior to the arytenoids and placement verified by bilateral breath sounds, capnography, and increasing oxygen saturations. The patient was hemodynamically stable throughout this period. Frothy secretions were suctioned from the endotracheal tube. The pH of these secretions was measured and found to be neutral.

• Surgery then proceeded without incident. Induction to delivery time was approximately 30 min; however, uterine incision to delivery time was within normal limits. An infant boy was delivered with Apgar scores of 1 at 1 min, 4 at 5 min and 9 at 10 min. The results of an umbilical venous blood gas test were pH 7.09, PCO2 86, PO2 13, HCO3 25.1, and a base deficit of -5.2, indicating an acute respiratory acidosis. The newborn was intubated and ventilated for 20 min until the respiratory acidosis was resolved and the anesthetic vapors exhaled. No further resuscitative measures were required……………………..

Propofol sensitivity

• Speedy H. Exaggerated physiological responses to propofol in myotonic dystrophy. Br J Anaesth 1990; 64:110-2. – <1 mg /kg of propofol was sufficient to induce hypnosis and permit

tracheal intubation.

• Gottschalk A,Heiman-Patterson T, deQuevedo R II;, Quinn PD..General Anesthesia for a Patient with Centronuclear (Myotubular) Myopathy.Anesthesiology 89:1018-20, 1998 – induced with propofol and maintained with a propofol infusion,

nitrous oxide, and oxygen. No additional intravenous medications were administered at any time, except for ketorolac 1 h before emergence.

– Bilateral coronoidectomies with bilateral arthroplasty with eminectomies were performed without difficulty. The surgical sites were infiltrated with bupivacaine by the surgeon. The patient awoke and was transported to the postanesthesia care unit while breathing spontaneously. After uneventful extubation, she was placed on nasal bilevel pressure-assisted ventilation at her usual settings.

Sasuga M, Matsukawa T, Ookawa I, Tamaki F, Masamune T, Kumazawa T. Anesthetic management of three patients with myotonic dystrophy in a family Masui. 2004; 53:269-72.• Case-1: A 24-year-old woman was admitted because of pressing hydramnion. She

was treated by ritodrine hydrochlorides leading to rhabdomyolysis, and she was diagnosed as myotonic dystrophy. She underwent cesarean section because of urgent premature birth. The surgery was performed with spinal anesthesia using tetracaine. Case-2: A 1-year-old boy, the son of Case 1, underwent orchiopexy. He showed respiratory distress at birth and needed respiratory support for 140 days. The surgery was performed under general anesthesia combined with caudal anesthesia. Anesthesia was induced with nitrous oxide-oxygen-sevoflurane. He was intubated without muscle relaxants. Since he recovered consciousness soon after the surgery, he was extubated and returned to the ward. Case-3: A 30-year-old woman, the sister of Case 1, underwent tonsillectomy. At the age of 27 she underwent salpingectomy under general anesthesia with nitrous oxide-oxygen-halothane, after which she was diagnosed as myotonic dystrophy. She was anesthetized with propofol and fentanyl. Because severity of the myotonic dystrophy varies among the patients, the strategy for anesthesia should be planned on each patient. Generally speaking, regional anesthesia including spinal and epidural anesthesia is preferable

Propofol in a case of myotonic dystrophy (Tzabar, Y.; Marshall, R.; Russell, S. H.Myotonic dystrophy and target–controlled

propofol infusions . Br. J. Anaesth. 1995; 74:108.

• 23–yr–old, 63–kg Caucasian male• admitted for operative fixation of a fractured mandible and suffering from myotonic

dystrophy• TCI set at 2 µg/ ml and increased in steps of 2 µg/ml Alfentanil 1 mg was

administered when verbal contact with the patient was lost.:when the target concentration reached 12 mg/ ml and the patient’s jaw was relaxed, laryngoscopy was performed and nasotracheal intubation easily accomplished .

• No neuromuscular blocker was used at any time.,but N2O was added intraoperatively. • Anaesthesia maintained with a TCI of 6 µg/ml which was reduced to 5 µg/ ml

after 30 min and 4 µg /ml at 60 min. Total operative time was 75 min. • Towards the end of the procedure the target concentration was set to 0 mg/ ml so that

the reduction in calculated propofol concentration could be followed. • The patient did not commence spontaneous respiration until the calculated propofol

concentration decreased to less than 2 µ g/ ml. Respiration was slow and shallow initially but improved with time. There were no signs of awakening or response to voice even when the predicted propofol concentration was less than 1 µ g/ ml. He was observed for a further 30 min with no change

• He was then transferred to the intensive care unit where he was observed while still breathing spontaneously through the tracheal tube, attached to a T–piece. Arterial oxygen saturation and end–tidal carbon dioxide remained satisfactory throughout. Approximately 1 h after the end of surgery, he began to show signs of awakening and extubated his own trachea. His subsequent postoperative course was uneventful and the following morning he was discharged to the general ward.

Bennun M,Goldstein B,Finkelstein Y,Jedeikin R.Continuous propofol anaesthesia for patients with myotonic dystrophy.Clinical Investigation. Br. J. Anaesth. 2000; 85:407-409 • 13 patients with myotonic dystrophy scheduled for oropharyngeal and neck

surgery, The median age was 21 yr (range: 11–42 yr). • enrolled in an open prospective study.• able to function adequately, with good physical mobility and without

handicap. • no history of systemic disease and none was taking medication.• Physical examination showed wasting of thenar and masseteric muscles.

Preoperative haematological and biochemical investigations, ECG, echocardiograpy and lung function tests were normal.

• . No pre-anaesthetic medication was administered.• Anaesthesia was induced with fentanyl 0.05 mg, propofol 2.5

mg kg-1 and atracurium 0.5 mg kg-1. After intubation of the trachea, the patients' lungs were ventilated with 70% N2O in oxygen and anaesthesia was maintained with a continuous infusion of propofol 6 mg kg-1 h-1, bolus fentanyl 2 µ g kg-1 and incremental doses of atracurium 0.2 mg kg-1. After patients had regained consciousness and four equal `train of four' twitches were observed, the trachea was extubated.

Results from Bennun• The mean (SD) duration of anaesthesia was 104 (44) min(

– Operations: pharyngeal flap for correction of velopharyngeal incompetence (8 pts)– pharyngeal flap and tonsillectomy (t2 pts)– endoscopic surgery of the sinuses (FESS) for pansinusitis (1)– cervical lymph node biopsy (1)– total thyroidectomy for papillary carcinoma of thyroid (1).

• mean (SD) recovery time was 12 (11.5) min. T• Ephedrine was not required in any case. • The mean postoperative SpO2 (97 (2.9)) did not differ from the preoperative (98 (1)) values. • The median hospital admission was 2 days (range: 1–4 days).

• There was no difference between mean preoperative and postoperative tidal volumes (334 (119) ml versus 330 (122) ml) (P=0.97).

• However, there was a significant decrease in mean postoperative vital capacity (965 (349) ml) from the preoperative value (1664 (566) ml) (P=0.0028).

• There were no perioperative respiratory or cardiac complications and bronchial secretions were not a problem.

• Only two patients complained of nausea and vomiting, but no treatment was required. Similarly, muscular hypertonia and shivering were not observed.

Johnson GW,Chadwick S,Eadsforth P, Hartopp I.Anaesthesia and myotonia.Br.J.Anaesth.1995;75:113.• • Ist 53–yr–old man with moderate myotonia dystrophica, ischaemic heart disease

(including myocardial infarction 1 yr previously) and marked peripheral vascular disease. He presented with an acute on chronic ischaemic leg, requiring urgent exploration of his femoral artery.

• Temazepam 10 mg was administered orally 1 h before operation. After preoxygenation, anaesthesia was induced with fentanyl 250 mg, propofol 50 mg (the effect noted), followed 1 min later by another 25 mg. A propofol infusion was then given at a rate of 6 mg kg-1 h-1 for 15 min, then 4 mg kg-1 h-1 for another 10 min and finally 2 mg kg-1 h-1 for the remainder of the operation. Atracurium 20 mg was also given. No other sedative or analgesic drugs were used. The patient underwent femoral embolectomy without any major problems.

• The propofol infusion was discontinued 55 min after induction. Within 3 min his respiratory efforts were adequate and the trachea was extubated. However, although respiration was satisfactory and the airway was well maintained, it was a further 65 min before verbal contact was made with the patient.

• The immediate postoperative period was uneventful but on day 7 he began to develop increasing weakness, including bulbar weakness, and he died on day 14.

•

Johnson GW,Chadwick S,Eadsforth P, Hartopp I.Anaesthesia and myotonia.Br.J.Anaesth.1995;75:113• The second case was a 27–yr–old female with moderately severe myotonia dystrophica

causing cataracts, marked muscle weakness, slurred speech and swallowing difficulties. However, she was mobile and had no respiratory or cardiovascular system involvement. She was admitted for laparoscopic cholecystectomy.

• The patient was premedicated with temazepam 10 mg, and heparin 5000 u. was administered s.c. After preoxygenation, fentanyl 100 mg was given and the effect observed. Three 25–mg increments of propofol were given at 1–min intervals to assess the patient's sensitivity to propofol. When it was evident that the patient was not sensitive, propofol 125 mg was given followed by atracurium 15 mg. Anaesthesia was maintained with 0.5–1.0% isoflurane and nitrous oxide in oxygen. The operation and anaesthetic proceeded uneventfully with a further 100 mg of fentanyl and 10 mg of atracurium being required. Morphine 10 mg was administered at the end of operation. The patient made a rapid recovery and was fit to leave theatre recovery 35 min after the anaesthetic.

• The third case was female with moderate myotonia undergoing total abdominal hysterectomy. She had mild muscle weakness with no other problems (she had only been diagnosed because of family screening.) After premedication with temazepam 10 mg, anaesthesia was induced with alfentanil 2 mg followed by propofol 140 mg given slowly. Intubation was performed without formal paralysis and anaesthesia was maintained with a propofol infusion of 10 mg kg-1 h-1 followed by 8 mg kg-1 h-1 followed by 6 mg kg-1 h-1 , and an infusion of alfentanil 1.5 mg h-1. The operation lasted 40 min and the patient rapidly regained consciousness. Her trachea was extubated within 5 min of termination of the infusions. She made an uneventful recovery and was fit to go to the ward within 45 min.

Myotonia caused by propofol

• generalized myotonic state was also reported after the i.v. administration of propofol. – Bouly A, Nathan N, Feiss P. Propofol in myotonic dystrophy.

Anaesthesia 1991; 46:705. • Regional myotonia:

– Kinney MAO, Harrison BA.Propofol-Induced Myotonia in Myotonic Dystrophy .Anesth Analg 1996; 83:665–6

• A 38-yr-old male, ASA physical status II, with myotonic dystrophy presented for removal of orthopedic hardware from the lumbar spine. Midazolam, 1.0 mg, and fentanyl, 100 mg, were given intravenously. General anesthesia was induced with 200 mg propofol (2.5 mg/kg). Immediately after the propofol, the patient described pain in his right arm causing flexion of his right arm. After loss of consciousness, a sustained contracture occurred in the right arm and lasted approximately 20 s before spontaneously relaxing. Anesthesia, emergence, and recovery were uneventful.

Ketamine

• Ketamine has been used as and adjunct to caudal anesthesia in a 2 years old child– Shiraishi M,Minami K, Kadaya T.A Safe Anesthetic Method

Using Caudal Block and Ketamine for the Child with conngenital Myotonic Dystrophy. Anesthesia & Analgesia 2002; 94:233.

• TIVA(ket/fent/ propofol) for laparoscopic cholecystectomy for cholelithiasis. – Kushikata T, Yatsu Y, Kubota T, Matsuki A.[Total

intravenous anesthesia with propofol, ketamine, and fentanyl (PFK) for a patient with mitochondrial myopathy. Masui. 2004 Feb;53(2):178-80

• .

Drug combinations

• An obese female presenting for coronary bypass grafting • known carrier of central core disease and therefore MH susceptible;• After ensuring full precautions to prevent and treat MH were in place, she was • premedicated with i.m. morphine 15 mg and metoclopramide 10 mg and oral lorazepam 3 mg, 1

h before surgery. • Anaesthesia was induced with midazolam 7 mg, fentanyl 20 micrg/ k and

pancuronium 16 mg. • Anaesthesia was maintained using a propofol infusion at 300-400 mg/ h. • Other infusions: dopamine , glyceryl trinitrate ,aprotinin 2 000 000 U was given at sternotomy,

followed by another 2 000 000 U during bypass. Anticoagulation was achieved with heparin (total dose 45 000 IU).

• The patient was cooled to 32C on cardiopulmonary bypass and the aortic cross-clamp time was 45 min.

• After bypass, the residual effects of heparin were reversed with protamine 375 mg. • 4 units of platelets and 2 units of fresh frozen plasma were transfused perioperatively. The

decision to transfuse blood products was made on account of increased microvascular bleeding. No allogenic blood was transfused at any time. After surgery, the patient was transferred to the intensive care unit and her trachea was extubated after 12 h. Postoperative recovery was uneventful. This patient did not show any sign of muscle weakness at any time in the postoperative period and was discharged from hospital after 8 days. Lung function tests and determination of serum CK concentration were not repeated.

Drug combinations

• patient severely compromised by MELAS syndrome – 20-yr-old man presenting for a right cochlear implant had a medical

history significant for MELAS syndrome. Between the ages of 1 and 5 yr, the only possible abnormality was delayed speech development. At the age of 7 yr, he was diagnosed with hearing loss. He began having episodes of dizziness and bilateral leg weakness at the age of 14 yr. Two years later, he experienced a generalized seizure. His continued neurologic deterioration led to his present condition of blindness, deafness, dementia, and severe muscle wasting.

• anesthetized successfully by a combination of midazolam,propofol,cisatracurium,fentanyl,droperidol.– Thompson VA,Wahr JA..Anesthetic Considerations in Patients

Presenting with Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS) Syndrome

Anesth Analg 1997; 85:1404-6.

Propofol-fentanyl• Uchiyama Y, Miyamoto E, Yamada M, Murao K, Nakao S, Shingu

K.Anesthesia for laparoscopic cryptorchidpexy in a patient with congenital myopathy.Masui. 2003;52:1107-9. – 18-month-old, 11.3-kg, male patient, who had received a diagnosis of CM,

was scheduled for the laparoscopic cryptorchidpexy. Anesthesia was induced with propofol and fentanyl, and the trachea was intubated without muscle relaxants. An epidural catheter was inserted via the sacral hiatus, the tip of which was located at the second lumbar level for a purpose of obtaining not only pain relief but also muscle relaxation. Anesthesia was maintained with propofol, nitrous oxide and fentanyl, combined with epidural anesthesia. The anesthetic course was uneventful with enough pain relief and good muscle relaxation.

• Sasuga M, Matsukawa T, Ookawa I, Tamaki F, Masamune T, Kumazawa T. Anesthetic management of three patients with myotonic dystrophy in a family Masui. 2004; 53:269-72.– I pt.anesth for tonsillectomy with propofol/fentanyl(

Ay B, Gercek A, Dogan VI, Kiyan G, Gogus YF. Pyloromyotomy in a patient with paramyotonia congenita.Anesth Analg. 2004; 98:68-9, •

A 2-mo-old infant with paramyotonia congenita was scheduled for pyloromyotomy and repair of inguinal hernia. Diagnosis of paramyotonia congenita was done with positive family history, myotonia at eyelids, provocation by cold, and electromyogram analysis. Anesthesia was induced via face mask with sevoflurane at 4 minimum alveolar anesthetic concentration in oxygen. Tracheal intubation was attempted without a neuromuscular relaxant. Anesthesia was maintained with sevoflurane at 0.5 minimum alveolar anesthetic concentration in oxygen and remifentanil infusion at a rate of 0.2 micro g. kg(-1). min(-1). After discontinuation of sevoflurane and remifentanil, the patient was awake and had full recovery of muscle activity. IMPLICATIONS: The literature concerning general anesthesia in paramyotonic patients is limited. We report a case of paramyotonia congenita in a 2-mo-old male infant undergoing surgery for pyloric stenosis and inguinal hernia after an uneventful anesthesia.

Balanced anesthesia for emergency surgery in a patient with myotonic dystrophyMarsh D F, Scott R C,Russell SH, Hirsch NP. Anaesthesia in myotonic dystrophy Br. J. Anaesth. 1994; 73:124

• A 37–yr–old women presented for surgery with a diagnosis of myotonic dystrophy. ….. Previous anaesthesia for minor elective gynaecological procedures had been uneventful. On examination she was obese and had prominent upper incisors with micrognathia.

• The patient was scheduled for appendicectomy and no premedication was given. Full monitoring was applied in the anaesthetic room and after preoxygenation for 5 min, anaesthesia was induced with alfentanil 0.5 mg mg followed by propofol 140 mg, with the application of cricoid pressure. OTI was achieved with the aid of a gum elastic bougie. Anaesthesia w;as maintained with isoflurane and 70% nitrous oxide in oxygen and the lungs were ventilated mechanically, without neuromuscular block. At the end of surgery, adequate spontaneous ventilation returned rapidly and the patient was transferred to the intensive care unit where an infusion of fentanyl was commenced. The trachea was extubated after return of consciousness and the patient made an uneventful recovery.

Problems of this patientMarsh D F, Scott R C,Russell SH, Hirsch NP. Anaesthesia in myotonic dystrophy Br. J. Anaesth. 1994; 73:124 .

• a potentially difficult patient with regard to tracheal intubation• e additional risk of aspiration of stomach contents after induction of

anaesthesia.• avoidance of suxamethonium is mandatory in patients with myotonic

dystrophy and thus a conventional rapid sequence induction could not be performed.

• It was thought that a regional technique would have been a suitable alternative, but was not an option because of patient refusal.

• An awake intubation was considered but places the patient at risk from aspiration.

• Inhalation induction might cause early upper airway obstruction because of her pharyngeal muscle weakness and obesity.

• Induction and intubation using alfentanil and propofol alone without the need for neuromuscular block have been described recently , but have not been reported previously in a patient with myotonic dystrophy. The new non–depolarizing neuromuscular blocker, rocuronium, provides rapid onset of good intubating conditions comparable with suxamethonium and may be a suitable alternative when freely available.

• We consider that the intubating conditions obtained with this technique were excellent and may be considered as an alternative to conventional rapid sequence induction in patients in whom suxamethonium is contraindicated.

Multimodal approach• patient affected by the the King-Denborough syndrome (KDS)a rare

disorder that is associated with myopathy, susceptibility to malignant hyperthermia (MH) as well as congenital skeletal and facial anomalies

• 24-yr-old primiparous woman with a diagnosis of KDS and a history of previous MH reaction (at age 2). Her KDS resulted in chronic respiratory failure,with a permanent tracheostomy and overnight ventilatory support for the previous two years. She had three admissions during her pregnancy, one for pneumonia and two for preterm labour. Labour was induced at 37 weeks. Her labour was managed in the operating room where a "clean" anesthesia machine was ready. Cooling aids and a MH emergency kit were immediately available. Intravenous access, an arterial line and a lumbar epidural catheter were inserted before induction of labour. Ropivacaine 0.08% + fentanyl 2 microg/ml were used for patient-controlled epidural analgesia. After 6.5 hr of labour the patient required ventilation. An outlet forceps was performed for delivery. Postpartum, she was ventilated overnight in the intensive care unit..– Habib AS, Millar S, Deballi P 3rd, Muir HA. Anesthetic management of a

ventilator-dependent parturient with the King-Denborough syndrome.Can J Anaesth. 2003 ;50:589-9.

Preoperative assessment:

• 1)Muscular system:– Fatigue– respiratory.;intra/postop !!response to

hypoxemia/hypercarbia/stress……… – swallowing

– Measurement of the pvO2 during aerobic forearm exercise provides an easily performed screening test that detects impaired O2 use and the severity of oxidative impairment in patients with mitochondrial myopathy and exercise intolerance

2:Respiratory

– Respiratory function is frequently compromised before surgery – patients are at a higher risk of post operative respiratory complications.– After surgery, the patient with Duchenne’s muscular dystrophy must be monitored closely for evidence

of pulmonary dysfunction and retention of pulmonary secretions. Vigorous respiratory therapy and ventilatory support may be necessary.

– A history of chest infections and apnoea should be sought . – Pulmonary flow volume loops, a chest X‑ray and blood gases are

indicated preoperatively in these patients– Respiratory depressants should be avoided with pre medication as

respiratory responses to hypoxaemia and hypercapnia are impaired .– Patients with progressive bulbar muscle involvement are especially

predisposed to aspiration :to reduce risk:• reduce gastric volume and acid secretion• keep the gastric pH >2.5 with the use of adequate (but not prolonged) fasting• nasogastric and percutaneous gastrostomy tube (aspiration of in case of

PEG)• histamine‑2 receptor antagonists• proton pump inhibitors • non‑particulate antacids

3:Cardiac

• cardiomyopathies (dilated and hypertrophic) – Dodds T M, Haney M F,Appleton F MManagement ofperipartum CHF using continuous

AV hemofiltration in a patuient with myotonic dystrophy.Anesthesiology 1991;75:907.

Case report of a woman in the third trimester of pregnancy with CHF from myotonic dystrophy-related cardiomyopathy; CAVH was used for the treatment of refractory CHF in preparation for operative delivery.

• pre‑excitation syndromes (Wolf Parkinson‑White)• conduction defects (heart blocks) • hypertension • Mitral valve prolapse(myotonia)

– A 12‑lead ECG should be performed preop.

– further work‑up using echocardiograph• There is increased risk of sudden death from conduction

abnormalities . Atrioventricular conduction blocks occur in patients with Kearns‑Sayer syndrome .

4:Liver & Metabolic• Liver function and hepatic mitochondrial redox potentials can be

measured by arterial /ven ketone body ratios, calculated by the ratio of acetoacetate to 3‑hydroxybutyrate

• . If the liver and kidneys are affected, this might lead to altered pharmacokinetics and pharmacodynamics of any drugs ---------careful drug dose titration!!

• Metabolic dysfunction due to liver involvement result in altered glucose, lactate and protein metabolism should be avoided an good hydration maintained

• Glucose management can be challengig requiring frequent assessment In the newborn glucose represents the sole energy supply to the heart

• In children, preoperative hypoglycaernia shoul be avoided by the i.v. infusion of glucose containing fluids or glucose‑containing solutions up to 3 h p induction

• The prevalence of diabetes is higher patients with mitochondrial myopathies

5:Liver & Metabolic

• Patients often have elevated serum lactate ev Although a raised lactic acid concentration not considered to be a specific test, it points to t diagnosis especially when significantly elevated [5 Lactic acidosis is usually worsened by stress .

• In mitochondrial myopathies, high lactate production m contribute to the decreased muscle function observ by inhibiting the production of interleukin‑6

• Any increases in metabolic stress that may provoke worsen lactic acidosis should be avoided.

• Adequate oxygenation and minimization of oxygen demand stable cardiovascular fiinctions, maintenance of norm serum glucose levels, and acid‑base and electrolyt balance help to minimize acidosis .

5:Neurologic

• Blindness

• Deafness

• Communication may be a problem in these patients due to sensory deprivation

• The presence a parent or guardian during induction is beneficial

• .

• Indeed, all body systems may be affected.

General recommendations• Monitoring should matched to the clinical state and the surgery

performed A basic minimum would be continuous electrocardio graph and pulse rate, non‑invasive blood pressure pulse oximetry, capnography and temperature monitoring;ABG recommended

• Temperature monitoring with a nasopharyngeal probe is essential to main tain normothermia All i.v. fluids and epidural local anaesthetic solutions should be warmed to body temp.

• It is advisable to avoid Ringer's lactate to prevent an exacerbation of lactic acidosis Maintaining normothermia (core and surface), normoglycaemia and avoiding metabolic stress are important in the perioperative management of these patients .

• In cardiac bypass, normothermia during the bypass avoids mitochondrial stress from hypothermia .

• LMA>ET?:anesth depth lighter,less or no muscle relaxants

General recommendations :2

• Aerobic metabolism is already dysfunctional and any increases in basic metabolic rate (such as Peri operative shivering) should be prevented

• Any increases in O2 consumption should be minimized by maintaining normal body temperature and ade quate surgical anaesthesia (either general or regional) should be provided

• A cardiovascularly stable anaesthetic is recommended .• Any anaesthetic agents that depress cardiovascular function

should be avoided. During spontaneous breathing, all oploids and sedative‑hypnotics should be carefully titrated due to the decreased ventilatory response to hypoxia and hypercarbia .

• Effective perioperative analgesia will avoid increases in metabolism, provide comfort and allow early ambulation .

• In spontaneously breathing patients, the cautious use of oploids is advised as oploids may further impair regulation of breathing and lead to a respiratory acidosis (in addition to any underlying metabolic acidosis

•

Analgesia

• A multimodal analgesic approach should be used involving the use of oploid administration (via i.v. infusion or patient‑controlled analgesia), non‑steroidal anti‑inflammatory drugs and the use of local anaesthesia at wound sites, peripheral nerves, regional plexuses and neuraxially.

• In labour and delivery in women with mitochondrial myopathies, the management should be individualized according to the severity of the disease and by multidisciplinary consensus. Epidural analgesia reduces stress and work associated with labour and reduces oxygen demand during labour . Patients with documented increased lactate concentrations at rest and exercise are best managed with elective Caesarean sections as soon as fetal lung maturity has been confirmed under regional anaesthesia to prevent life‑threatening lactic acidosis during labour .

• Butler MG,Hayes BG, Hathaway M,Begleiter M L., Specific genetic diseases at risk for sedation/anesthesia complications.Anesth.Analg 2000;91:837-855

• • ABSTRACT: We reviewed of a number of genetic diseases known or at risk

for sedation or anesthesia complications. Some of these conditions are relatively common (e.g., Down's syndrome) whereas others are rare or present with multiple congenital anomalies that have an impact on health care delivery. We listed complications, recommended presedation evaluations, and included checklist items to assist the health care provider administering sedation and anesthesia. A better recognition and awareness of risk factors associated with specific genetic diseases should lessen the likelihood of complications during these procedures.

Reviews…..• Wappler F. Current aspects of anesthesia in neuromuscular

diseasesAnasthesiol Intensivmed Notfallmed Schmerzther. 2003 Jul;38(7):495-9. Review. German. No abstract available. Bischoff P. [Which diagnostics are essential in patients with neuromuscular diseases?]Anasthesiol Intensivmed Notfallmed Schmerzther. 2003 Jul;38(7):488-91. Review. German. No abstract available. Rosenkranz T. [Myopathies--what does the anesthetist need to know?]Anasthesiol Intensivmed Notfallmed Schmerzther. 2003 Jul;38(7):483-8. Review. German. No abstract available. Wappler F, Schulte am Esch J. Anaesthesia in patients with neuromuscular diseases--new concepts for old problems?Anasthesiol Intensivmed Notfallmed Schmerzther. 2003 Jul;38(7):470-1. English, German. No abstract available.

• uropean Journal of Anaesthesiology 2004; 21: 173‑178

• Review

• Mitochondrial myopathies and anaesthesia

• E. A. Shipton, D. 0. Prosser• University of Otago, Christchurch School of Medicine

and Health Sciences, Department of Anaesthesia,• Christchurch, New Zealand

THE END

Boring,but clinical…………….