Malignant Hyperthermia Tariq H. Khan Consultant Anesthesiologist / Pain Specialist KRL Hospital Islamabad Editor-in-Chief ‘Anaesthesia, Pain & Intensive Care’

Layout plan Real life scenarios Concerns Options & Suggestions

First Scenario 1998, Armed Forces Institute of Urology Rawalpindi A 4 year old child Ectopic vesicae GA Preoxygenation Pentothal + Succinyl choline Monitoring SpO2 + NIBP No expert help available

First Scenario Jaw rigidity Inability to open the mouth Dropped SpO2 Irregular SpO2 trace Forced intubation done + 100% O2 + vaporiser removed Cardiac monitor applied straight line Resuscitation failed

Second Scenario Year 2001, CMH Badin 11 years old boy Inguinal herniotomy Caudal block + GA Propofol + N2O + O2 LMA Trace of halothane Gradual rigidity of the full body Stopped halothane Gradual relaxation Halothane again Gradual rigidity Stopped halothane Gradual relaxation

Third Scenario An adult 52 years old male Known hypertensive Reduction of fracture Lt elbow Dormicum + Nalbuphine + Etomidate I-gel size 4 inserted Patients jerky movements Atracurium + isoflurane + Paracetamol Patient stabilised

EtCO2 started rising from 40-45 mmHg to 57 mmHg SpO2 95-96% Minute ventilation increased No effect Upper torso warm to touch and lower limbs cold Hyperventilation manually with 100% O2 No effect I-gel No. 4 replaced with No. 5 Difficult mouth opening + Rapid desaturation + Help called EtCO2 up to 60 mmHg 80 mmHg

Surgery postponed + Patient supine + ETT passed with difficulty EtCO2 up to 90 mmHg >100 mmHg Body temperature 104○ F 106○ F. Maximum 107.2○ F Anesthesia machine changed + New Bain circuit 100% O2 + Hyperventilation manually Body surface cooling + ice cold saline through Foley catheter and NG tube After four hours shifted to ICU ventilator

Cooling

Gradually temperature came down EtCO2 came down Next day patient weaned off Cardiac status checked No residual damage Neurological status checked No residual damage CK came down over next three days Patient reoperated after five days with vaporizer free and ventilator free machine Discharged after seven days

Fourth scenario Cleft camp at Gujrat (UK-Pak team) 2 years old girl operated developed hyperthermia in the recovery room Not responded to paracetamol Responded to dantrolene Saved

MH across the world 3 children died of MH during 17 years in PIMS Islamabad; (Rana Imran Sikander) One child in Mayo Hospital Lahore ENT; Died (Ambreen Khan) 2 children died at Faisalabad 25 case in Toronto Hospital (Canada) developed MH during 15 years Saved due to availability of dantrolene, (Nusrat Saleem) One case in Turkey; saved by dantrolene (Hasan Özkaya) 2 cases in 25 years. 1 survived, (Zia Uddin Kakepoto)

USA Frequency ranges from 1 in 10,000 patients receiving anesthetics to 1 in 50,000 The reported frequency in children is higher. M:F ratio is higher 291 MH episodes recorded in the North American Malignant Hyperthermia Registry database between 1987 and 2006 Estimated genetic prevalence may be up to 1 : 2,000-3,000 because MHS is inherited as an autosomal dominant trait

Mortality Mortality reduced from 70-80% to 5% with dantrolene USA: There were 8 cardiac arrests and 4 deaths, and the median age of patients experiencing cardiac arrest or death was 20 years 1 or 2 deaths are reported to the MH hotline each year UK: 0-2 reported deaths per year

Morbidity Morbidity rate: 34.8% renal dysfunction (97.3%) changes in the consciousness level/coma (9.8%) cardiac dysfunction (9.4%) pulmonary edema (8.4%) disseminated intravascular coagulation (7.2%), and hepatic dysfunction (5.6%)

Pathophysiology Triggers; Volatile anesthetics; Succinyl choline A subclinical myopathy large quantities of calcium released from the sarcoplasmic reticulum (SR) of skeletal muscle and cause a hypermetabolic state Raised temperature > 105○ F Rising EtCO2 >100 mmHg Muscle rigidity Dysrrhythmias

Differential Diagnoses Heatstroke Cystnosis Hyperthyroidism MODS in Sepsis Osteogenesis imperfecta Pheochromocytoma Prader-Willi Syndrome Rhabdomyolysis Wolf-Hirschhorn Syndrome

Molecular Genetic Testing >30 mutations 30% of patients with known MH have one of these mutations.  RYR1 (the gene coding for the ryanodine receptor in skeletal muscle) is associated with as many as 50-60% of MH cases in families Mutation of CACNA1S is responsible for 1% of all cases of MH susceptibility.

Management Dantrolene Discontinuation of triggering agents Call for help Stop the surgical procedure Cooling Hyperventilation with oxygen Early treatment of hyperkalemia Monitoring in ICU for 24-48 hours

Dosage 2.5 mg/kg rapid IV bolus, repeat PRN >10 mg/kg (cumulative dose) is necessary (up to 30 mg/kg) Maintenance: 1 mg/kg IV q4-6hr OR 0.25 mg/kg/hr IV infusion Average patient uses a median dose of 5.9 mg/kg of dantrolene sodium in a crisis

Cost

Cost Dentrium (20 mg per vial) = 720 ml $65 x 36 = $2340 = Rs. 2,34,000 Ryanodex (250 mg per vial) = 5 ml $2300 x 3 = $6900 = Rs. 6,90,000

Prognosis If an MH reaction is treated early in the process, complete recovery can be expected. Multiple organ failure and death can occur Before dantrolene in the late 1970s, the mortality of an acute MH reaction was greater than 70% Currently, the mortality of acute MH is less than 5%

Suggestions PSA should approach Health ministries for appropriate legislation PSA should celebrate an MH day every year PSA should maintain an MH Registry to get all actual or suspected MH cases registered

Suggestions Divide each big city into 4 zones at least (according to no. of hospitals and accessibility). There should be 1 set of Dantrolene in each zone.

Suggestions Alternatively, dantroline should be made available at Military Hospitals nearest to Corps HQ Rawalpindi; Peshawar; Lahore; Multan; Karachi; Quetta; Gilgit; (Kharian; Gujranwala; Bhawalpur) Air lift the drug by helicopters to the required site Evacuation of the patient to bigger medical centers if required

Suggestions MH squads may also be designated Maintain an MH box in all operating room complexes

Invitation Let us save the mothers and children Maternal mortality in Pakistan > 250 per 100,000 live births. Italy 3,9; UAE 8.2; Japan 6.8 SpO2, EtCO2 and defibrillators must be made available at all THQ / DHQ hospitals PSA + Apicare Journal + Pakistani Anesthesiologists abroad Collaboration with LIFEBOX Donations + Database + Procurement & Supply Public-Private partnership model

Questions & Comments Please!