Spectrum of Severity and Prevalence of Malignant Hyperthermia in

Anesthetized Patient with Inhalational Anesthetics

Research Thesis

Submitted By

Muhammad Imran: (235/BPMI/BS-2017)

Abrar Khan: (225/BPMI/BS-2017)

Sohail Muhammad: (246/BPMI/BS-2017)

Aman Ullah: (227/BPMI/BS-2017)

Naseer Ahmad: (239/BPMI/BS-2017)

BS Anesthesia Technology

SUPERVISOR: IRSHAD KHAN

Bashir Institute of Health Sciences Affiliated with Shaheed Zulfiqar Ali Bhutto
Medical University (SZABMU) PIMS Islamabad

i
 Dedication

This project is dedicated to God Almighty, our creator, our pillar of strength, our source of

inspiration, wisdom, knowledge, and understanding. Throughout this initiative, he has been our

source of strength, and We have only been able to fly on his wings. This work is also dedicated

to our parents and family. Our dear and respected instructors Mr. Irshad Khan, who have always

encouraged us and ensured that We give everything We have to finish what We have started.

Thanks to our dear friends and respected seniors who supported us in tough situation to complete

this task. Thank you everybody, and may God continue to bless you all.

ii
 Acknowledgement

All praise and thanks to Allah who endowed us with will, strength, and means to complete

this thesis. Without His bounty, grace and mercy this work would have never been

accomplished.

We would like to express our sincere gratitude to our supervisor Mr. Irshad Khan for the

Continuous support of our bachelor study and research, for his patience, motivation,

enthusiasm, And immense knowledge. His guidance helped us in all the time of research and

writing of this thesis. we would not have imagined having a better mentor for our bachelor

study. However, it will not be possible without the kind support and help of many individuals

and Shaheed Zulfiqar Bhutto Medical University, Islamabad. We would like to extend our

sincere thanks to all of them.

Last but not the least, we would like to thank our family: to be there at first place and

supporting us spiritually throughout our life.

Muhammad Imran

Abrar khan

Sohail Muhammad

Aman Ullah

Naseer Ahmad

BS AT

iii
 DECLARATION

We hereby declare that the material printed in this study is our own work and has not printed,

submitted to any journal for publication.

Muhammad Imran

Abrar khan

Sohail Muhammad

Aman Ullah

Naseer Ahmad

BS Anesthesia Technology

iv
Table of Contents

Dedication.............................................................................................................................................ii
Acknowledgement...............................................................................................................................iii
DECLARATION................................................................................................................................iv
LIST OF ABBREVIATIONS............................................................................................................vii
List of Table.......................................................................................................................................viii
ABSTRACT.........................................................................................................................................x
Background:.......................................................................................................................................x
Objective:...........................................................................................................................................x
Methodology:....................................................................................................................................xi
Results:.............................................................................................................................................xi
Conclusion:.......................................................................................................................................xi
CHAPTER 1........................................................................................................................................1
INTRODUCTION...............................................................................................................................1
1 Background................................................................................................................................1
1.1 Research Gap / Problem........................................................................................................6
1.2 Research Question.................................................................................................................7
1.3 Objectives of Study................................................................................................................7
1.4 Definitions of Study Variables...............................................................................................8
1.4.1 Prevalence of Malignant hyperthermia:.............................................................................8
1.4.2 Inhalational Anesthetic Agent:...................................................................................8
1.4.3 Severity of Malignant Hyperthermia.........................................................................8
CHAPTER 2......................................................................................................................................10
LITERATURE REVIEW.................................................................................................................10
CHAPTER 3......................................................................................................................................16
Materials and Methodology..............................................................................................................16
3.1 Study Design........................................................................................................................16
3.2 Study Site and Setting..........................................................................................................16
3.3 Study Duration.....................................................................................................................16
3.4 Study Participants................................................................................................................16
3.5 Sampling Size......................................................................................................................16
3.6 Sampling Technique............................................................................................................16
3.7 Study procedure...................................................................................................................17
3.8 Inclusion Criteria.................................................................................................................17
3.9 Exclusion criteria.................................................................................................................17

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 3.10 Ethical consideration............................................................................................................17
3.11 Data Analysis.......................................................................................................................18
CHAPTER 4......................................................................................................................................19
RESULTS...........................................................................................................................................19
4.1 Demographic Analysis.........................................................................................................19
4.3 Prevalence of malignant hyperthermia.......................................................................................20
4.5 Association of MH with other variables....................................................................................21
4.6 Association of malignant hyperthermia with age.......................................................................21
4.6 Severity of malignant hyperthermia...........................................................................................22
CHAPTER 5......................................................................................................................................23
DISCUSSION.....................................................................................................................................23
CONCLUSION...............................................................................................................................25
LIMITATION AND FUTURE RECOMMENDATION.................................................................25
IMPLICATION...............................................................................................................................26

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 LIST OF ABBREVIATIONS

 SZABMU: Shaheed Zulfiqar Ali Bhutto Medical University.

 SPSS: Statistical Package for The Social Science.

 MH: Malignant Hyperthermia.

 GA: General Anesthesia.

 FDA: The Food and Drug Administration.

 ETCO2: End-tidal CO2.

 PACO2: Partial pressure of CO2

List of Tables

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Table 1: Summary of Scales with Number of Items................................................................13

Table 2:Frequency of Genders.................................................................................................14

Table 3 For frequency of age...................................................................................................15

Table 4 Total number of cases.................................................................................................16

Table 5 Prevalence rate of malignant hyperthermia................................................................16

Table 6 Association of malignant hyperthermia with gender..................................................17

Table 7 Association of malignant hyperthermia with age.......................................................17

List of Figure

viii
Figure 1..............................................................................................................................................22

ix
 ABSTRACT

Background: Malignant hyperthermia (MH) is a pharmacogenetic syndrome that variably

expresses itself on exposure to triggering agents like inhalational anesthetics and
suxamethonium. Prevalence of Malignant Hyperthermia in Islamabad is not well
documented. In this study, we assessed the Spectrum of Severity and Prevalence of
Malignant Hyperthermia in Anesthetized Patient with Inhalational Anesthetics in Islamabad
hospitals.

Objectives: The main objectives of this research study were to find out prevalence of
malignant hyperthermia. To assess the spectrum of severity of malignant hyperthermia, and
to analyze the association of each triggering agent with induction rate. To analyze spectrum
of severity malignant hyperthermia in patient anesthetized with inhalational anesthetic agents.

Methodology: This was retrospective study on spectrum of severity and prevalence of

malignant hyperthermia in anesthetized Patient with Inhalational anesthetics. Data collected

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of previous year June 2020 to June 2021 in eight tertiary care hospitals of Islamabad. Total
40900 patients were discharged under general anesthesia.

Results: Of the total number of 40900 patient discharges from 8 tertiary care hospitals of
Islamabad. During the study period,7 patients had a recorded diagnosis of MH due to
anesthesia. MH is associate with gender (male and female) in which the male ratio is higher
than female. There were 4 males and 3 female patient diagnose. The percentage of male was
57.14 and female was 42.86%. The percentage of prevalence rate of malignant hyperthermia
was 0.018%.

Conclusion: This research study concluded that the prevalence rate of malignant
hyperthermia in Islamabad is 0.018%. The prevalence rate male is slightly higher than
female. As according to this statement the total number of male patient who got malignant
hyperthermia was four and female was three out of total 40900 surgical cases under general
anesthesia in specific one year of duration. The prevalence of MH due to anesthesia in
surgical patients treated in Islamabad hospitals is approximately 1 per 5842 cases. MH risk in
males is significantly higher than in females.

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 CHAPTER 1

INTRODUCTION

Anesthesia is a situation in which a patient temporarily loss the awareness of his sensation for

medical purposes. It might incorporate a few or all of absence of pain (help from or

counteraction of agony), loss of motion (muscle unwinding), amnesia (loss of memory), and

obviousness [1]. The aim of anesthesia is to achieve the points required for surgical

procedure with the least risk to the patient. Anesthesia generally use for patient during

surgical procedure [2]. General anesthesia is a medically induced coma with loss of

protective reflexes, resulting from the administration of one or more general anesthetic

agents. It is carried out to allow medical procedures that would otherwise be intolerably

painful for the patient, or where the nature of the procedure itself precludes the patient being

awake [3].

A variety of drugs may be administered, with the overall aim of ensuring unconsciousness,

amnesia, analgesia, loss of reflexes of the autonomic nervous system, and in some cases

paralysis of skeletal muscles. The optimal combination of drugs for any given patient and

procedure is typically selected by an anesthetist, or another provider such as intensives,

anesthetist practitioner, physician assistant, or nurse anesthetist (depending on local practice),

in consultation with the patient and the surgeon, dentist, or other practitioner performing the

operative procedure. General anesthesia is usually induced in an operating theatre or in a

dedicated anesthetic room adjacent to the theatre [3].

Anesthetic agents may be administered by various routes, including inhalation,

injection (intravenous, intramuscular, or subcutaneous), oral, and rectal. Once they enter the

circulatory system, the agents are transported to their biochemical sites of action in the

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central and autonomic nervous systems. Most general anesthetics are induced either

intravenously or by inhalation. Intravenous injection works faster than inhalation, taking

about 10–20 seconds to induce total unconsciousness. This minimizes the excitatory phase

(Stage 2) and thus reduces complications related to the induction of anesthesia. Commonly

used intravenous induction agents include protocol, sodium thiopental, etomidate,

methohexital, and ketamine. Inhalational anesthesia may be chosen when intravenous access

is difficult to obtain (e.g., children), when difficulty maintaining the airway is anticipated, or

when the patient prefers it.

Sevoflurane is the most commonly used agent for inhalational induction, because it is

less irritating to the tracheobronchial tree than other agents. As an example sequence of

induction drugs: Pre-oxygenation to fill lungs with oxygen to permit a longer period of apnea

during intubation without affecting blood oxygen levels, Switching from oxygen to a mixture

of oxygen and inhalational anesthetic (Sevoflurane, Desflurane, Isoflurane, Halothane,

Enflurane). Surgical procedure requiring analgesia and muscle relaxation that cannot be

performed using regional anesthesia techniques. The indication of general anesthesia are

upper abdomen surgeries, thoracic surgery, head and neck surgery shoulder surgery etc.

surgical procedure that significantly interfere with vital functions: neurosurgery, thoracic

surgery, cardiac surgery, surgery of aorta etc. The advantages of anesthesia are Reduces

patient awareness to the surgical procedure, proper muscle relaxation, and control of the

airway, breathing, and circulation, rapid administration, easy procedures & prolonged

sedation in a single setting.

There are some specific conditions that increase the risk for patient which undergoing

general anesthesia such as: obstructive sleep apnea, a condition where individuals stop

breathing while asleep, seizures, existing heart, kidney or lung conditions, high blood

pressure, alcoholism, smoking, history of reactions to anesthesia and malignant hyperthermia.

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Malignant hyperthermia is the most lethal risk factor of general anesthesia. Malignant

hyperthermia (MH), also called malignant hyperpyrexia, is an autosomal dominant genetic

disorder of the skeletal muscle. This condition is a pharmacokinetic syndrome that variably

expresses itself on exposure to triggering agents, which include inhaled volatile anesthetics

(e.g., halothane, isoflurane, Enflurane, and sevoflurane) and depolarizing muscle relaxants

(e.g., succinylcholine). MH is characterized by signs of hyper metabolism caused by the

release of calcium from the sarcoplasmic reticulum, increased oxygen consumption, and

increasing and unexplained increase in end-tidal CO2 that does not decrease with increasing

minute ventilation, tachycardia, muscle rigidity, hyperthermia, and respiratory and metabolic

acidosis. Other signs of MH may include disseminated intravascular coagulation, cardiac

arrhythmias, hyperkalemia, hypophosphatemia, hypocalcaemia, rhabdomyolysis,

myoglobinuria, and mottled skin [4, 5]. The aim of this research is to identify the range of

severity and prevalence of malignant hyperthermia in patient anesthetized with inhalational

anesthetic agent. Malignant hyperthermia (MH) is a rare, yet potentially fatal disorder caused

by exposure to inhalational anesthetics (e.g., halothane, isoflurane, sevoflurane, Desflurane,

etc) and succinylcholine which is use in general anesthesia [6].

This severe reaction typically includes a dangerously high body temperature, rigid

muscles or spasms, a rapid heart rate, and other symptoms. Increase end tidal carbon dioxide

Skeletal muscle rigidity, Muscle spasm, Tachycardia ,Metabolic and respiratory acidosis,

Tachypnea ,sweating the risk factor is if one of your parents has the abnormal gene, we have

a 50% chance of having it too (autosomal dominant inheritance pattern).If we have other

relatives with this genetic disorder, your chance of having it is also increased our risk of

having malignant hyperthermia is also higher if you or a close relative has a history of an

event that is suspected to be malignant hyperthermia during anesthesia a history of muscle

tissue breakdown called rhabdomyolysis, which can be triggered by exercise in extreme heat

3
and humidity or when taking a statin drug Certain muscle diseases and disorders caused by

inherited abnormal genes. The prevention is if you have a family history of malignant

hyperthermia or a relative who has problems with anesthesia, tell your doctor or

anesthesiologist before surgery or any procedure that requires anesthesia. The incidence of

MH episodes during anesthesia is between 1:10,000 and 1:250,000 anesthetics [7, 8]. Even

though an MH crisis may develop at first exposure to anesthesia with those agents known to

trigger an MH episode, on average, patients require three anesthetics before triggering.

Reactions develop more frequently in males than females (2:1) [9].

All ethnic groups are affected, in all parts of the world. The highest incidence is in

young people, with a mean age of all patients experiencing reactions of 18.3 years. It has

been found that children under 15 years age comprised 52.1 % of all reactions [10]. Although

described in the newborn, the earliest reaction confirmed by testing is six months of age [11].

The oldest is 78 years. Evaluating risk of malignant hyperthermia allows your

anesthesiologist to avoid certain anesthesia drugs. The prevalence of malignant

hyperthermia according to the Survey of Medical Institutions 2008 in Japan, the number of

surgeries under general anesthesia performed throughout Japan was 187,097 per month. the

survey included 1,238,171 patients during a total of 18 months, which represented

approximately 36.8%(1,238,171/18/187,097) of all surgeries under general anesthesia in

Japan. the results showed the actual prevalence of MH (13.7 per 1 million) in the Japanese

population between 2006 and 2008, which was similar to the roughly estimated figure (16.7

per 1 million) presented in a previous Japanese report [12]. Our study was the first to

confirm the actual nationwide prevalence of MH, based on large-scale cross-sectional data.

On the other hand, 12,749,125 patient discharges from New York State hospitals during

2001 through 2005, 73 patients had a diagnosis of MH due to anesthesia [4]. For 38 of the

73 cases, the MH diagnosis was marked as the condition being present at admission. For the

4
 remaining 35 cases, the diagnosis referred to events that occurred during the index

hospitalization.

The overall prevalence of MH related to exposure to anesthesia was 0.57 per 100,000

hospitalizations, 0.96 per 100,000 surgical discharges, 1.08 per 100,000 discharges in which

there was any indication of anesthesia, and 4.39 per 100,000 nonsurgical therapeutic

procedures requiring anesthesia [4]. The main objective of this research study is to determine

the prevalence of malignant hyperthermia in patient anesthetized with inhalational anesthetic

agents, spectrum of severity of malignant hyperthermia in patient anesthetized with

inhalational Anesthetic agents and association of each triggering agent with induction rate

and spectrum of severity malignant hyperthermia in patient anesthetized with inhalational

anesthetic agents. The peripheral nerves connect the spinal cord to the rest of our body [13].

The main advantages of anesthesia are reducing patient awareness to the surgical

procedure, proper muscle relaxation, control of the airway, breathing, and circulation, rapid

administration, easy procedures & prolonged sedation. The specific risks of anesthesia vary

with the kind of anesthesia, type of surgery (elective or emergent), and patient specific

factors, including age and pre-existing medical conditions. The malignant hyperthermia

causes some complications such as Respiratory depression, Stroke, Hypoxic brain injury

cardiovascular collapse, cardiac arrest and Death. Malignant hyperthermia is a severe

reaction to certain drugs used for anesthesia. This severe reaction typically includes a

dangerously high body temperature, rigid muscles or spasms, a rapid heart rate, and other

symptoms. Without prompt treatment, the complications caused by malignant hyperthermia

can be fatal. The significance of this research study is to determine the incidence of malignant

hyperthermia due to inhalational anesthetic in general anesthesia [14].

1.1 Research Gap / Problem

5
The prevalence of malignant hyperthermia due to anesthesia in surgical patients treated in

New York State hospitals is approximately 1 per 100,000. Malignant hyperthermia risk in

males is significantly higher than in females. No single drug was significantly associated with

the occurrence of malignant hyperthermia. Data should be continuously compiled, and further

analyses with larger numbers of cases are necessary to identify possible causative agents.

Malignant hyperthermia remains a serious risk factor for susceptible individuals undergoing

general anesthesia using volatile agents. A number of environmental stresses have also been

implicated as risk factors in malignant hyperthermia individuals but there is as yet no clear

consensus from the literature. While two genes have been unequivocally linked to causation

of malignant hyperthermia, discordance exists and the potential for the involvement of other

genes cannot be discounted. The incidence of death due to malignant hyperthermia has

decreased in the last thirty years but at the same time the prevalence of genetic variants in the

general population has been estimated to be much higher than was originally thought. In

addition, unresolved issues including discordance “awake” malignant hyperthermia and the

influence of statin therapy suggests that genetic variants previously associated mainly with

anesthetic-induced malignant hyperthermia may have a much wider range of pathological

phenotypes. As a final comment, mortality in malignant hyperthermia has been reduced from

80 % to 1.4 % although a recent report shows a further increase so there is still a significant

mortality from this disorder and vigilance must be maintained with any anesthetic where

triggering drugs are administered. Malignant hyperthermia has spectrum of severity which is

the main gap of this research study. The gap will analyze after data collection and data data

analyze.

1.2 Research Question:

This research project strives to find the possible answers of following questions:

6
 1. What is the prevalence of malignant hyperthermia in patient anesthetized with

inhalational anesthetic agents?

2. What is the spectrum of severity of malignant hyperthermia in patient anesthetized

with inhalational Anesthetic agents?

3. What is the association of each triggering agent with induction rate and spectrum of

severity malignant hyperthermia in patient anesthetized with inhalational anesthetic

agents?

1.3 Objectives of Study

The main objectives of this research study are:

1. To find out prevalence of malignant hyperthermia in patient anesthetized with

inhalational anesthetic agents

2. To assess the spectrum of severity of malignant hyperthermia in patient anesthetized

with inhalational anesthetics.

3. To analyze the association of each triggering agent with induction rate and spectrum

of severity malignant hyperthermia in patient anesthetized with inhalational anesthetic

agents

1.4 Definitions of Study Variables

The research study involves following variables. Their definitions with appropriate

references are being provided here.

1.4.1 Prevalence of Malignant hyperthermia: Malignant hyperthermia is a severe

reaction to certain drugs used for anesthesia.MH has been reported in every country,

and all races are susceptible. MH occurs more frequently in males than females and

7
 more commonly in children and young adults with the mean age of 18.3 years. This

severe reaction typically includes a dangerously high body temperature, rigid muscles

or spasms, a rapid heart rate, and other symptoms. Malignant hyperthermia occurs in 1

in 5,000 to 50,000 instances in which people are given anesthetic gases.

1.4.2 Inhalational Anesthetic Agent: An inhalational anesthetic is a chemical compound

possessing general anesthetic properties that can be delivered via inhalation. They

are administered through a face mask, laryngeal mask airway or tracheal tube

connected to an anesthetic vaporize and an anesthetic delivery system.

1.4.3 Severity of Malignant Hyperthermia: The severity of this severe reaction

typically includes a dangerously high body temperature, rigid muscles or spasms, a

rapid heart, tachypnea, hyperkalemia and other symptoms. Without prompt

treatment, the complications caused by malignant hyperthermia can be fatal.

8
 CHAPTER 2

LITERATURE REVIEW

Masahiko Sumitani et al 2011 stated that Malignant hyperthermia (MH) is a rare but

life-threatening disease that occurs during general anesthesia. The actual prevalence of MH

remains unclear, and the association between MH and various anesthetic drugs remains

controversial because of a lack of universal reporting and succinylcholine which is use in

general anesthesia [15].

Masahiko Sumitani et al 2011 stated that mortality and morbidity have decreased over the

past several decades, MH will continue to be of potential concern to clinicians whenever

inhalational anesthetic agents or succinylcholine is used. MH has been reported in every

country, and all races are susceptible [15].

Orphanet 2015 et al stated that MH occurs more frequently in males than females and more

commonly in children and young adults with the mean age of 18.3 years. MH is a genetic

disorder of skeletal muscle calcium regulation in humans, linked to the ryanodine receptor

type 1 (RYR1) gene. Many studies from the past report an incidence of MH ranging from

1:10,000 to 1: 220,000. This suggests that the incidence of MH is difficult to estimate due to

its rarity and limited data. In addition, the incidence of MH seems to vary, depending on the

geographic region, age, gender, and race. Systematic reviews and meta-analysis have been

increasingly used to formulate public health policies and to guide resource allocation to

improve population health outcomes [16].

The case fatality rate of MH has decreased to less than 5% with dantrolene therapy and

advanced intraoperative monitoring techniques However, the costs involved with continuous

temperature monitoring and stocking dantrolene owing to its 3-year shelf-life limit, as well as

9
the relatively high cost of the drug can also be issues that may govern the formulation of

public health policies. Further, the paucity of epidemiologic data on MH leads to uncertainty

regarding its true incidence, which limits analysis of cost-effectiveness. Thus, the primary

objective of this systematic review and meta-analysis is to determine the incidence of MH in

patients undergoing general anesthesia. Further, this review will attempt to evaluate trends in

the incidence of MH. Data on the incidence of MH across different geographical regions,

different age groups, gender, and race will also be analyzed [16].

PM Hopkins 2011 et al stated that Nitrous oxide, intravenous induction agents,

benzodiazepines, opioids, and the non depolarizing relaxants do not trigger MH. Malignant

hyperthermia triggered by exposure to volatile anesthetic gases (e.g., Desflurane, Enflurane,

halothane, Sevoflurane) or the depolarizing muscle relaxant, succinylcholine. The clinical

manifestation of malignant hyperthermia includes Increase end tidal carbon dioxide Skeletal

muscle rigidity, muscle spasm, tachycardia, Metabolic and respiratory acidosis, Tachypnea,

Sweating, Cardiac arrest, hyperkalemia or hypocalcaemia, elevated CPK elevated

temperature, mottled cyanosis (Patchy, irregular skin color) and myoglobinuria. Malignant

hyperthermia has an underlying genetic basis, and genetically susceptible individuals are at

risk of developing malignant hyperthermia if they are exposed to any of the erased

sympathetic nervous system outflow [17].

PM Hopkins 2011 et al stated that most consistent manifestation of potent inhalational

anesthetics or suxamethonium. Increased intermediary metabolism results in increased

oxygen consumption and carbon dioxide production, which in turn causes increased

sympathetic activity is an increasing heart rate. The blood pressure response in MH is more

variable as this balances the effects of sympathetic stimulation with the peripheral vasodilator

consequences of metabolic by-products. Increased metabolic rate will also produce heat,

10
leading to an increasing body temperature as the heat dissipates from the skeletal muscle

[15].

JE Brady 2009 et al. The prevalence of MH due to anesthesia in surgical patients treated in

New York State hospitals is approximately 1 per 100,000. MH risk in males is significantly

higher than in females.MH has no pathognomonic features, the cardial clinical features result

from excessive carbon dioxide production. This will manifest in the mechanically ventilated

patient as increased ETCO2 (even with attempts by the anesthetist to control ETCO2 by

increasing minute ventilation) or in the spontaneously breathing patient as an increase in

respiratory rate and subsequently increased ETCO2. An unexplained, unexpected increase in

carbon dioxide production should alert the anesthetist to the possibility of an MH reaction.

The true incidence of MH susceptibility has not been precisely established in the United

States because of the lack of universal reporting and the fact that many MH-susceptible

persons have not been exposed to a triggering agent [4].

JE Brady 2009 et al. stated that MH occurs globally in all ethnic groups. Reactions are

reported to occur more frequently in males than in females, and patients younger than 19

years’ account for approximately 50% of reported events. The mortality rates of MH

dramatically decreased from 70-80% to 10% after an introduction of dantrolene sodium for

the treatment of MH, and recent mortality is estimated to be less than 5% with early detection

of MH episode using capnography, prompt use of the drug dantrolene, and the introduction of

diagnostic testing. Although the mortality rates of MH are low, the morbidity rate of MH is

much higher [4].

According to the recent study of Larach et al 1989, the morbidity rate of MH is 34.8% and

frequently reported complications are changes in the consciousness level/coma (9.8%),

cardiac dysfunction (9.4%), pulmonary edema (8.4%), renal dysfunction (97.3%),

11
disseminated intravascular coagulation (7.2%), and hepatic dysfunction (5.6%). This high

morbidity rate emphasizes the need for continuing education of anesthesiologists on the most

effective way to diagnose and treat MH. The following treatment should be start immediately

when patient suspected to malignant hyperthermia. Discontinue inhalational agent or

succinylcholine, hyperventilate with 100% oxygen, bicarbonate 1_2 mg/kg as needed,

dantrolene 2.5mg/kg push, treat arrhythmia (do not use calcium channel blocker) arterial or

venous blood gases and cool patient; surface and wound [5].

Larach et al 1989 stated that Indications for treatment of MH include signs of hyper

metabolism, rapid increase in carbon dioxide (metabolic acidosis may be delayed),

tachycardia, and muscle or jaw rigidity. Patients may not present with all of these clinical

signs, but without a persuasive alternative diagnosis, it is recommended that dantrolene be

initiated and triggering agents be discontinued immediately rather than waiting too long to do

so, which could lead to a negative outcome [5].

Kanji Uchida et all 2009. No single drug was significantly associated with the occurrence of

MH. Data should be continuously compiled, and further analyses with larger numbers of

cases are necessary to identify possible causative agents. According to the Malignant

Hyperthermia association of United State, these four things should be done as soon as

possible in treating an acute MH event. Notify the surgeon to terminate the procedure as soon

as possible and discontinue volatile agents and succinylcholine. Obtain the dantrolene/MH

cart; if at a surgical center rather than a hospital, call 911.Hyperventilate the patient with

100% oxygen at 10 L/minute. Administer dantrolene. IV dantrolene is the only drug FDA-

approved for the treatment of MH. Dantrolene is a hydration-derivative skeletal muscle

relaxant that acts by directly interfering with the release of calcium from the sarcoplasmic

reticulum [18].

12
PM Hopkins 2011 et al stated that during an MH reaction, triggering agents produce a change

in the patient’s skeletal-muscle cells, resulting in elevated mycoplasma calcium; dantrolene is

thought to prevent or reduce this increase, which activates the acute catabolic processes

associated with MH.16 Dantrolene is an isotonic solution with a half-life of 4 to 11 hours.

The initial dose recommended by the MHAUS is 2.5 mg/kg, with the dose continuously

repeated until symptoms subside; large doses (>10 mg/kg) may be required in some patients,

and it is suggested that an alternative diagnosis be considered if large doses of dantrolene do

not resolve symptoms. There are two available formulations of dantrolene. Dantrium and

Revonto, the older formulation, provide 20 mg of dantrolene sodium/60 ml after

reconstitution in sterile water. Dantrium and Revonto should be reconstituted by adding 60 ml

of Sterile Water for Injection (without a bacteriostatic agent), and the vial should be shaken

until the solution is clear [15].

Kanji Uchida et all 2009 stated that the newer formulation, Ryanodex, is an injectable

suspension of dantrolene sodium that provides 250 mg of dantrolene sodium/5 ml after

reconstitution. Each vial of Ryanodex should be reconstituted with 5 ml of Sterile Water for

Injection (without a bacteriostatic agent) and shaken to ensure a uniform, opaque, orange-

colored suspension. It is recommended that blood gases be tested to determine the degree of

metabolic acidosis, and the provider should consider administering sodium bicarbonate at a

dosage of 1 to 2 mEq/kg for a base excess greater than –8, for a maximum dosage of 50 mEq

[18].

13
Patients with MH should be cooled if their core temperature is greater than 39°C or is

rapidly rising; cooling should be stopped when the temperature is less than 38°C. Patients

with hyperkalemia should be treated with calcium chloride 10 mg/kg (maximum dose

2,000 mg) or calcium gluconate (maximum dose 3,000 mg), sodium bicarbonate 1 to 2

mEq/kg IV (maximum dose 50 mEq), glucose, and insulin (pediatric patients, 0.1 U

regular insulin/kg IV and 0.5 g/kg dextrose; adult patients, 10 U regular insulin IV and 50

mL 50% dextrose), and glucose levels should be checked hourly. In the case of refractory

hyperkalemia, albuterol, kayexelate, dialysis, or extracorporeal membrane oxygenation

should be considered if a patient has experienced cardiac arrest. Dysrhythmias should be

treated with standard medications; however, calcium channel blockers must be avoided

during an MH crisis because they can worsen hyperkalemia and hypotension. Patients

having an MH reaction should be diuresis to greater than 1 mL/kg/hour urine output; if

creatinine kinase (CK) or potassium rises, myoglobinuria should be suspected and a

bicarbonate infusion of 1 mEq/kg/hour should be initiated to alkalinize the urine [18].

Kanji Uchida et all 2009 stated that It is important to appropriately monitor patients

experiencing an MH reaction, including monitoring of core temperature and urine output

Once the initial MH reaction is under control and the patient is stable, the patient should be

continuously monitored in a post anesthesia care unit or ICU for at least 24 hours

Indications that a patient is stabilizing are normal or declining end-tidal carbon dioxide

levels, decreased or stable heart rate with no signs of dysrhythmias, resolving

hyperthermia, and no generalized muscular rigidity Immediately following an acute MH

14
 reaction, dantrolene should be continued for at least 24 hours at a dosage of 1 mg/kg by IV

injection every 4 to 6 hours or by IV infusion at a dosage of 0.25 mg/kg/hour [18].

CHAPTER 3

Materials and Methodology

3.1 Study Design

Retrospective study design was used.

3.2 Study Site and Setting

Study was carried out at Rawalpindi and Islamabad eight tertiary care Hospitals.

All data was collected by researcher on visiting hospitals.

3.3 Study Duration

The study was conducted from 1st September to December 2021.

3.4 Study Participants

All surgical procedure under general anesthesia patient visiting eight tertiary care hospitals

of Rawalpindi and Islamabad for treatment purposes.

3.5 Sampling Size

A random selection of 40900 patients of eight tertiary care hospitals of Rawalpindi and

Islamabad

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3.6 Sampling Technique

Non-probability random convenient sampling Technique was used for data collection.

3.7 Study procedure

A intraoperative audit of 40900 patients undergoing general anesthesia of eight tertiary care

hospitals of Rawalpindi and Islamabad were included in this study. These patients were

studied on the basis of spectrum of severity and prevalence of MH in anaesthetize patient

with inhalational anesthetics.

3.8 Inclusion Criteria

1. Patient whose age is above 10 years.

2.Patient whose age below 60 years.

3.Patient undergoing general anesthesia.

3.9 Exclusion criteria

1.Patient use suxamethonium

2.Patient below 10 years.

3.Patient above 60 years.

3.10 Ethical consideration

Ethical consideration for this study was taken from ethics & research committee of BIHS.

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3.11 Data Analysis

Data has been analyzed using statistical software (SPSS) version 25.

 Continuous data has been expressed as mean ± standard deviation to analyze

Chi-square and correlation test was applied to ordinal and continuous data respectively to

access relationship between different variables.

Independent T-test was applied to compare means of 2 groups.

Table 1. 1: Summary of Scales with Number of Items

Table 1: Summary of Scales with Number of Items

No Variable Source No of Item

1 Prevalence of malignant [19] Age, Gender and Marital
hyperthermia Status
2 Inhalational anesthetic agent [19] 07 items
3 Severity of malignant [20] 15 items
hyperthermia
We have prepared this questionnaire in the presence and supervision of an expert in
research work

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 CHAPTER 4

RESULTS

4.1 Demographic Analysis:

We calculated the percentage and frequency of total suspected MH cases in which the
frequency of male is 4 is higher than female which is 3. The percentage of male suspected
cases is 57.14% and female is 42.86%. As shown in the table 1.

Table 2: Frequency of Genders

Frequency Pe
rcent
Male 4 57.
14
4.2
Female 3 42.86
Total 7 100.0
Frequency of age:

This table shows age and frequency of patient.in the table we have seven patient of different
age. The age of seven MH suspected patient is 8,23,24,28,33,43 and 55. The percentage of all
seven patients 100 and 14.3 is individually for every patient.

Table 3: For frequency of age

Age F Percent
requency
8 1 14.3
23 1 14.3

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 24 1 14.3
28 1 14.3
33 1 14.3
43 1 14.3
55 1 14.3
Total 7 100

4.2 Descriptive Analysis:

This table show total cases from June 2020 to June 2021 in eight main hospitals at Islamabad
with minimum 1520, maximum 9360 and mean 5112.5.

Table 4 Total number of cases

N Minimum Maximum Mean

Cases 40900 1520 9360 5112.5

4.3 Prevalence of malignant hyperthermia.

Prevalence =Number of cases /total number of cases X 100

= 7/40900 X 100

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 =0.018%

4.4: Prevalence rate of malignant hyperthermia

This tables show the prevalence rate of malignant hyperthermia in total cases. The total
surgical cases under GA are 40900 with total seven MH suspected cases. So the total
Prevalence rate is 0.018% shown in the table.

Table 5: Prevalence rate of malignant hyperthermia

Total surgical cases under Total MH cases Prevalence rate

GA

40900 7 0.018%

4.5 Association of MH with other variables

Table 4.5: Association of malignant hyperthermia with gender.

This table show association of malignant hyperthermia with gender. In given table the MH is
associate with gender (male and female) in which the mal ratio is higher than female. There
are 4 males and 3 female patient were suspected.

Table 6: Association of malignant hyperthermia with gender

Gender

Male Female Total

MH 4 3 7

4.6 Association of malignant hyperthermia with age.

Table 4.6. In this table MH is associated with age in which we have seven different age of
patient. The age of seven MH suspected patient is 8,23,24,28,33,43 and 55 years.

Table 7: Association of malignant hyperthermia with age

Age Age Total

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 8 23 24 28 33 43 55

MH 1 1 1 1 1 1 1 7

4.6 Severity of malignant hyperthermia.

This chart shows the severity of malignant hyperthermia in total suspected patient out of total
surgical cases. The chart show the temperature, paco2, muscle tightness, respiratory rate and
heart rate the temperature is greater than 98.6F, the paco2 is greater than 45 mmhg, there was
muscle tightness during surgery, respiratory rate was higher than 25 and the heart rate was
more than 100b/m.

Figure 1:

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 CHAPTER 5

DISCUSSION

This study revealed that the prevalence of malignant hyperthermia is very rare in

Islamabad Pakistan. There were 40900 total surgical cases operated under general anesthesia

from June 2020 to June 2021 in eight tertiary care hospitals of Islamabad with minimum

1520, maximum 9360 and mean 5112.5. This research study showed that only seven

diagnosed cases of MH were reported out of 40900 surgical cases under general anesthesia.

The Prevalence rate of malignant hyperthermia was 0.018%. In other study 12,749,125

patient discharges from New York State hospitals during 2001 through 2005,73 patient

diagnosis of MH due to anesthesia. For 38 of the 73 cases, this study shows the frequency of

total malignant hyperthermia cases of male versus female is 4:3. The percentage of male

diagnosed cases were 57.14% and female is 42.86% [4].

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 This finding was also demonstrated by Masahiko et al in Japan. A total of

1,238,171surgical patients, who underwent general anesthesia, were identified during the

survey period, including 344,224 (27.8%) in teaching hospitals and 893,947 (72.2%) in

community hospitals. Overall, 48% of patients were men, and 18%were man and 82%

women. they identified 17 patients with a diagnosis of MH during the study period the

Prevalence rate of malignant hyperthermia were 0.00138 [15].

Although MH prevalence rates varied by the denominator type, higher rates for males were

seen across risk groups. The estimated prevalence of MH for males was 2.5–4.5 times the rate

for females depending on the denominator used. The difference of MH prevalence between

sexes was statistically significant at P 0.05 level for all risk groups [15].

Our research study demonstrated that frequency of male was 4 and female was 3 in total

suspected MH cases. Our study also revealed that the percentage of male suspected cases is

57.14% and female is 42.86% in total suspected MH cases. In conformity to the findings of

the current study, a work was done by Masahiko Sumitani which showed that men were three

times more likely to contract MH than women. The prevalence of MH was relatively high in

patients aged younger than 30 year compared with those older than 30 yr. These results

coincide with recent Japanese and American reports [15].

This research study showed the spectrum of severity which revealed that the temperature is

higher than 98.6 °F, the PaCo2 is more than 45 mmhg, there was muscle tightness during

surgery, respiratory rate was higher than 25 and the heart rate was also more than 100b/m.

This finding was also demonstrated in a research study by Brady, J.E In Japan, the original

MH criteria established by the Japan Society of Anesthesiologists are widely used and consist

of two elements: body temperature increase (more than 40°C or more than 38°C with a

23
markedly increasing rate and other clinical presentations of MH (e.g., tachycardia,

arrhythmia, metabolic acidosis, muscle rigidity, and Myoglobinuria) [4].

CONCLUSION

This research study concluded that the prevalence rate of malignant hyperthermia in

Islamabad is 0.018%. The prevalence rate of male is slightly higher than female. As

according to this statement the total number of male patient who got malignant hyperthermia

were four and female were three out of total 40900 surgical cases under general anesthesia in

specific one year of duration. All patient suffering from malignant hyperthermia were have

severe symptoms of temperature high than 98.6F the PaCo2 is more than 45 mmhg there was

muscle tightness during surgery, respiratory rate was higher than 25 and the heart rate was

also more than 100b/m.

LIMITATION AND FUTURE RECOMMENDATION

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 This research study was conducted at tertiary care hospitals of Islamabad. This research

study should be conducted to overall Pakistan and all provinces in upcoming researcher. This

research study was conducted at retrospective manner. The data was opted from previous one

year from June 2020 to June 2021. Future researcher should conduct this research study in the

prospective and observational manner to examine the prevalence rate of malignant

hyperthermia. This research study was only dependent on numerical data of past one year.

Upcoming researcher should involve the biomedical lab and investigation of patient suffering

from malignant hyperthermia. They should analyses muscle rigidity, temperature higher than

98.6F, the PaCo2 more than 45 mmhg, respiratory rate was higher than 25 and the heart rate

more than 100b/m.

25
REFERENCES:

1. Devi, S., M. Muki, and J. Chand, ANESTHESIA AND ITS APPPLICATION.

2. Pölönen, P., et al., A prospective, randomized study of goal-oriented hemodynamic therapy
in cardiac surgical patients. Anesthesia & Analgesia, 2000. 90(5): p. 1052-1059.
3. Roy, K., et al., Efficacy of preoperative melatonin and ramelteon (melatonin agonist) therapy
on dose requirement of propofol for induction of general anaesthesia: A comparative
prospective study. Indian Journal of Clinical Anaesthesia, 2020. 7(1): p. 172-176.
4. Brady, J.E., et al., Prevalence of malignant hyperthermia due to anesthesia in New York State,
2001–2005. Anesthesia & Analgesia, 2009. 109(4): p. 1162-1166.
5. Larach, M.G., Standardization of the caffeine halothane muscle contracture test. Anesthesia
& Analgesia, 1989. 69(4): p. 511-515.
6. Lindholm, P., et al., Development of malignant hyperthermia during cardiopulmonary
bypass. Journal of cardiothoracic and vascular anesthesia, 2000. 14(5): p. 576-578.
7. Hadzic, A., X. Sala-Blanch, and D. Xu, Ultrasound guidance may reduce but not eliminate
complications of peripheral nerve blocks. The Journal of the American Society of
Anesthesiologists, 2008. 108(4): p. 557-558.
8. Ording, H., Incidence of malignant hyperthermia in Denmark. Anesthesia and analgesia,
1985. 64(7): p. 700-704.
9. Riazi, S., et al., Malignant hyperthermia in Canada: characteristics of index anesthetics in 129
malignant hyperthermia susceptible probands. Anesthesia & Analgesia, 2014. 118(2): p. 381-
387.
10. Strazis, K.P. and A.W. Fox, Malignant hyperthermia: a review of published cases. Anesthesia
and analgesia, 1993. 77(2): p. 297-304.
11. Gonsalves, S.G., et al., Using Exome Data to Identify Malignant Hyperthermia Susceptibility
Mutations. Anesthesiology, 2013. 119(5): p. 1043-1053.
12. Suyama, H., M. Kawamoto, and O. Yuge, Prevention and treatment of malignant
hyperthermia in certified training hospitals in Japan: a questionnaire. Journal of anesthesia,
2002. 16(3): p. 207-210.
13. Dirksen, S.J.H., et al., Future directions in malignant hyperthermia research and patient care.
Anesthesia and analgesia, 2011. 113(5): p. 1108.
14. Misal, U.S., S.A. Joshi, and M.M. Shaikh, Delayed recovery from anesthesia: a postgraduate
educational review. Anesthesia, essays and researches, 2016. 10(2): p. 164.
15. Sumitani, M., et al., Prevalence of malignant hyperthermia and relationship with anesthetics
in Japan: data from the diagnosis procedure combination database. The Journal of the
American Society of Anesthesiologists, 2011. 114(1): p. 84-90.
16. Pena, M.J., et al., Special low protein foods for phenylketonuria: availability in Europe and an
examination of their nutritional profile. Orphanet journal of rare diseases, 2015. 10(1): p. 1-
6.
17. Hopkins, P., Ultrasound guidance as a gold standard in regional anaesthesia. 2007, Oxford
University Press. p. 299-301.
18. Uchida, K., et al., Granulocyte/macrophage–colony-stimulating factor autoantibodies and
myeloid cell immune functions in healthy subjects. Blood, The Journal of the American
Society of Hematology, 2009. 113(11): p. 2547-2556.
19. Bitan, D.T., et al., Fear of COVID-19 scale: Psychometric characteristics, reliability and validity
in the Israeli population. Psychiatry Research, 2020. 289: p. 113100.
20. Lepak, D.P. and S.A. Snell, Examining the human resource architecture: The relationships
among human capital, employment, and human resource configurations. Journal of
Management, 2019. 28: p. 517-543.

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