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

2. Layout plan
Real life scenarios
Concerns
Options & Suggestions

3. 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

4. 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

5. 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

6. 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

7. EtCO2 started rising from 40-45 mmHg to 57 mmHg
SpO %
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 mmHg

8. 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

10. Cooling

12. 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

13. 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

15. 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)

16. 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

17. 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

18. 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%)

19. 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

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

21. 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.

22. 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 hours

26. 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

28. Cost

29. 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

32. 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%

33. 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

34. 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.

35. 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

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

38. 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

39. Questions & Comments Please!