








































Anesthesia eJournal
Volume 4 - Issue 1 2016

AEJ

Educated Hand Publishing LLC 
“The Science Behind the Art”  

 Anesthesia eJournal - Online
ISSN 2333-2611

Page 20

Anesthetic Management of a Patient With Mitochondrial Encephalopathy, Lactic 
Acidosis, and Stroke-Like Symptoms (MELAS): A Case Study
Annabelle Flanagan DNP, CRNA
Affiliation:
Texas Christian University, email: Annabelle.H.Flanagan@gmail.com

Dennis Cheek PhD, RN
Affiliation:
Texas Christian University, email: d.cheek@tcu.edu

Funding/Conflict of Interest Disclosure: 
None

KEYWORDS: MELAS, mitochondrial disorders, anesthetic management, mitochondrial myopathy

INTRODUCTION
Mitochondrial myopathies (MMs) represent a wide range of defects in the mitochondria.1 Mitochondrial 

encephalopathy, lactic acidosis, and stroke-like symptoms (MELAS) syndrome is a type of mitochondrial disease that is 
systemic in nature.2 This is because of the multiple functions mitochondria serve in oxidative phosphorylation. MELAS 
has been speculated to affect respiratory enzyme complexes I and IV, which are essential in converting substrates from 
glycolysis, fatty acid oxidation, and the tricarboxylic acid cycle to ATP.1,3 

This disease is thought to pass maternally and to result from a mutation in mitochondrial DNA.1,2 Because MELAS 
involves a mitochondrial defect in aerobic metabolism, the disease has implications for anesthesia management. 
Anesthetic medications, surgery itself, and fasting in preparation for surgery can all increase the metabolic burden, 
leading to possible exacerbations in tissues dependent on large amounts of oxygen, such as the heart, muscle, and central 
nervous system.4,5 MMs have also been speculatively linked to malignant hyperthermia owing to the similar presentation 
of symptoms. Controversy exists, however, over whether anesthetic management should be based on concerns to avoid 
malignant hyperthermia triggers. 

Abstract
Mitochondrial encephalopathy, lactic acidosis, stroke-like symptoms (MELAS) syndrome is a specific mitochondrial 

myopathy that results in defects in respiratory enzyme complexes I and IV. This ultimately causes defects in aerobic 
metabolism, especially in high-energy-requiring organs, leading to an obvious concern with anesthetic management. 
Some mitochondrial myopathies have speculative linkages to malignant hyperthermia. This case report examines the 
anesthetic implications for a patient with MELAS. A 39-year-old man with MELAS underwent a right hip fracture 
pinning. The patient was successfully managed with a general endotracheal anesthetic using a propofol infusion and 
<1 minimum alveolar concentration of sevoflurane gas. The patient was extubated without complications. Anesthetic 
implications for the management of patients with MELAS include a tailored preoperative assessment because of the 
different phenotypical presentations of mitochondrial diseases. The metabolic burden in MELAS patients can be 
reduced by avoidance of the following: lactate in intravenous fluids, hypothermia, prolonged fasting, and postoperative 
nausea vomiting. Varied anesthetic techniques have been documented in multiple case reports. Careful titration of 
muscle relaxants and opioids is paramount to prevent postoperative respiratory failure. According to the Malignant 
Hyperthermia Association of the United States, avoidance of volatile anesthetics is not necessary in patients with 
mitochondrial myopathy.

mailto:Annabelle.H.Flanagan@gmail.com
mailto:d.cheek@tcu.edu


Anesthesia eJournal                         www.anesthesiaejournal.com
Volume 4 - Issue 1 2016 Page 21

CASE SUMMARY 
A 39-year-old Hispanic male, with a weight of 49 kg and a 

height of 157 cm, presented with a right hip fracture. The surgical 
procedure planned for this patient was a right hip fracture 
pinning. His previous medical history included a cerebrovascular 
accident in 2008 apparently while operating a motor vehicle. 
Immediately before this motor vehicle accident, the patient 
had blurry vision and a subsequent seizure. Upon admission to 
the hospital after the motor vehicle accident, a muscle biopsy 
was performed and the myopathy MELAS was discovered. The 
patient’s other medical conditions included hearing loss, diabetes, 
and an unsteady gait related to the motor vehicle accident. The 
patient’s medications included aspirin, insulin, pantoprazole, 
carbamazepine, zonisamide, co-enzyme Q10, iron, loratadine, 
and morphine. He was assessed as having an airway classification 
of Mallampati II, with a 4-fingerbreadth oral excursion and 
thyromental distance, normal upper and lower dentition, and 
normal neck extension and flexion. He had no known allergies to 
food or drugs. 

A review of his symptoms was essentially negative. The results 
of his physical exam were unremarkable other than a Foley 
catheter that was in place and musculoskeletal decompensation 
from a worsening gait with no assistive device use. A 22-guage 
intravenous catheter was started in the right antecubital vein with 
an infusion of lactated Ringer’s solution. The serum complete 
blood count showed a slightly elevated white blood cell count of 
9.2 and a hemoglobin level of 11.9 g/dL. However, the results of 
the basic metabolic panel and coagulation studies were all within 
normal limits. His preoperative vital signs included blood pressure 
of 121/77 mm Hg, heart rate of 90 beats per minute, normal 
sinus rhythm, respiratory rate of 16 breaths per minute, and skin 
temperature of 37.2 degrees Celsius. His American Society of 
Anesthesiologists classification was designated as a III.

The anesthetic plan for this patient included administration of 
preoperative medications of midazolam 4 mg and ondansetron 
4 mg for anxiolysis and prevention of postoperative nausea and 
vomiting. General endotracheal anesthesia was instituted by use 
of a conventional Macintosh laryngoscope blade (Welch Allyn, 
Skaneateles Falls, NY), the muscle relaxant cisatracurium 20 
mg, and the induction agents of propofol 50 mg, lidocaine 1% 
60 mg, and sufentanil 15 mcg. After securement of the airway, 
another large-bore intravenous catheter and an arterial catheter 
were started before the start of the case. Maintenance anesthesia 
was continued with a propofol infusion set initially to 50 mcg/
kg/min, sevoflurane at a goal end tidal concentration of 1.5, <1 
minimum alveolar concentration (MAC), and boluses of 10 mcg 
of sufentanil as needed. The patient was to be woken up fully on 
emergence with evidence of eye opening, spontaneous ventilation, 
and sustained head lift to ensure adequate return of respiratory 
drive prior to extubation. 

Upon arrival in the operating room, the patient was 
preoxygenated with 100% oxygen for 2 minutes with 10 L oxygen 
through a mask. Pre-induction vital signs were heart rate of 92 
beats per minute, normal sinus rhythm, skin temperature of 36 
degrees Celsius, noninvasive blood pressure of 111/82 mm Hg, 
and SpO2 of 100% as measured by pulse oximetry. Intravenous 
induction medications included those mentioned previously in 
the anesthetic plan. Induction was initiated with a conventional 

Macintosh 3 laryngoscope blade. Upon visualization of the 
airway, a Cormack-Lehane grade 4 was assessed. A gum elastic 
bougie tube introducer was passed with successful placement 
of a size 7.5-mm endotracheal tube. Confirmation of adequate 
placement was by auscultation of equal bilateral breath sounds, 
bilateral chest rise, and positive end tidal carbon dioxide at 39 
mm Hg. Sevoflurane gas was turned on to 1.5% with an end tidal 
concentration of 1.0 with 2 L of oxygen. The patient was placed 
on volume control mode on the mechanical ventilator with a tidal 
volume of 400 mL, rate of 10 breaths per minute, and positive 
inspiratory pressure of 14 mm Hg. Immediately after, another 
18-gauge peripheral intravenous catheter in the left arm and a 
20-gauge right radial catheter were started, 1 g of cefazolin was 
administered intravenously, and a propofol infusion was started. A 
forced air warmer and an intravenous fluid warmer were used to 
maintain patient normothermia. 

The intraoperative course remained uneventful. Sufentanil 
boluses of 10 and 15 mcg were given for pain control as well as 
100-mcg boluses of Neo-Synephrine (phenylephrine) to help 
maintain systolic blood pressure > 90 mm Hg. No additional 
muscle relaxant was given. Acetaminophen 1 g was also 
administered intravenously before the end of the case. The total 
crystalloid for the procedure was 1200 mL of lactated Ringer’s 
solution. Foley catheter output was 300 mL of dark amber urine. 
Estimated blood loss was minimal at 50 mL. Upon emergence, 
the patient was extubated awake, was spontaneously ventilating 
for 30 minutes with no pressure support, with eye opening, and 
with sustained head lift to 10 L of oxygen via a non-rebreather 
face mask at an end tidal sevoflurane concentration of 0.3.

DISCUSSION
MMs were first discovered 56 years ago in a patient who 

had large amounts of mitochondria in skeletal muscle.3 These 
diseases cause a wide range of clinical problems, including Leber’s 
hereditary optic neuropathy, chronic progressive ophthalmoplegia, 
Kearns-Sayre syndrome, myoclonic epilepsy and ragged-red fiber 
disease, and MELAS.3 The anesthetic management of patients 
with MMs such as MELAS is complicated for many reasons 
involving genetic inheritance and mutation as well as the varying 
phenotypic presentations of these diseases. The same genetic 
mutation in mitochondrial DNA may have different phenotypes 
in different patients, while different genetic mutations can also 
cause overlapping phenotypes.3 Thus, the safe use of an anesthetic 
technique in a patient with one mitochondrial defect may not 
translate to equal safety across other mitochondrial diseases with 
identical mutations.5

One of the genetic mutations that has been attributed to 
MELAS has been identified as MTTL1*MELAS3243G in 
the tRNALeu that affects complex I of the respiratory enzyme 
complexes involved in oxidative phosphorylation.3 This mutation 
in mitochondrial DNA when present in a high percentage 
is associated with stroke-like activity but when present in a 
low percentage is associated with diabetes and deafness.3 The 
patient in the present case report interestingly had stroke-
like activity, deafness, and diabetes. Another source identifies 
the affected respiratory complex as complex IV; other sources 
identify multiple mitochondrial DNA gene (tRNA and mRNA) 
mutations and deletions responsible for MELAS.1,4,6 The patient 



in the present case did not have a genetic report and the inability 
to obtain muscle biopsy records from his previous hospital 
admission made it difficult to determine the exact inheritance 
method and specific clinical presentation. Sources do, however, 
identify MELAS inheritance as being maternal in nature.2 

Diagnosis of MELAS must be individualized.6 Most MMs 
follow a slow and progressive course; thus, clinical investigations 
must be integrated by the same practitioner.4 Integrative 
diagnosis includes clinical, electrophysiological, imaging, 
biochemical, and genetic investigations.5 Genetic studies should 
be the first-line method for diagnosis after clinical features 
such as diabetes, deafness, and cardiomyopathy together raise 
red flags.6 After genetic studies, blood, urine, and cerebrospinal 
fluid studies should be conducted. If the results of these are 
negative, electrophysiological and neuroimaging studies should 
be performed in organs other than the nervous system.6 Last, 
a muscle biopsy and biochemical investigations should be 
conducted for diagnosis if the results of all other testing are 
negative. These investigations can include electron microscopy 
and respiratory chain enzyme analysis of the muscle.6,7 

There is no known cure for MELAS. One study showed 
marked improvement in stroke-like symptoms after 
administration of L-arginine, and more recently, exercise 
programs have been shown to prevent muscle deconditioning.7 
Other treatments include nutritional support with vitamins and 
cofactors; emotional therapy; physiologic stress reduction, such as 
environmental temperature control; and reducing toxin exposure, 
such as smoking.8

The clinical presentation of MELAS varies tremendously, and 
its incidence is rare: 12.5 cases per 100,000.2 Most importantly 
for anesthesia management, the respiratory chain is the final 
common pathway essential for aerobic metabolism. Patients 
present with symptoms that are dependent on tissues requiring 
large amounts of oxygen, such as the heart, central nervous 
system, and muscle.1 According to the Online Mendelian 
Inheritance in Man database, the general manifestations of 
MELAS range from “seizures, hemiparesis, hemianopsia, cortical 
blindness, to episodic vomiting.”9 Specific central nervous 
system manifestations of MELAS can also include psychiatric 
abnormalities, neuropsychological deficits, stroke-like episodes, 
migraines, epilepsy, ataxia, and hypopituitarism.4 MMs can affect 
a single organ system or multiple organ systems as in MELAS. 
Other organ system manifestations in MELAS can include 
cardiomyopathies, Wolff-Parkinson-White syndrome, cardiac 
conduction pathway blockade, diabetes mellitus, sensorineural 
hearing loss, gastrointestinal dysfunction, malnutrition, and 
muscle wasting.2 Preoperative evaluation of these patients 
must include tests specific to each organ system involved. 
Cardiomyopathy is most commonly present in MELAS; thus, a 
12-lead electrocardiogram and echocardiogram are paramount. 7 
The patient in this case report denied any cardiac history and thus 
this was not obtained in the preoperative evaluation but may have 
been helpful in developing an appropriate anesthetic plan. 

Other preoperative evaluation should include renal, hepatic, 
and blood glucose tests.10 A full neurologic evaluation should 
be conducted because MELAS patients can have stroke-like 
episodes mostly affecting the occipital and parietal lobes.4 
Exercise tolerance, swallowing, and respiratory functions are other 

considerations preoperatively, which may include chest x-ray 
imaging and pulmonary function tests.10

As a result of the inability of pyruvate to be integrated into 
the tricarboxylic acid cycle, MELAS patients have increased 
susceptibility to lactic acidemia under increased metabolic stress.4 
Therefore, general anesthesia, medications used for anesthesia, 
and surgery can cause deterioration of clinical manifestations 
in MMs because of increased metabolic stress.4 Other 
circumstances that can cause a metabolic burden in these patients 
and should be avoided or decreased include prolonged fasting, 
hypoglycemia, postoperative nausea and vomiting, hypothermia, 
prolonged tourniquets, acidosis, and hypovolemia.5 Choice 
of fluids in MELAS patients remains controversial because 
whereas hypoglycemia can cause increased metabolic burden, 
glucose-containing fluids may not be optimal for avoidance of 
seizures.5 In one case report, glucose-containing fluid was given 
intraoperatively in a MELAS patient without adverse effect.11 
Also, owing to the predisposition of these patients to lactic 
acidosis, lactated Ringer’s solution may not have been the best 
choice of intravenous fluids in this patient.11,12

According to the Malignant Hyperthermia Association of 
the United States (MHAUS), the first association between 
MMs and malignant hyperthermia was suggested owing to the 
similar presenting clinical features, such as acidosis.13 However, 
recommendations from MHAUS state that avoidance of volatile 
anesthetics is not necessary because of no increased susceptibility 
of patients with MMs to malignant hyperthermia.13 Avoidance 
of succinylcholine has been discussed because of one case report 
in 1985 in which life-threatening hyperkalemia occurred in a 
patient with mitochondrial dysfunction after its administration.13 
However, just as MHAUS suggests, no definitive genetic link has 
been shown between malignant hyperthermia and mitochondrial 
diseases such as MELAS.14 Only central core disease, multi-
minicore disease, and King-Denborough syndrome have a 
more definitive link to malignant hyperthermia.14 The use of 
succinylcholine in MELAS patients with muscle wasting can 
still predispose patients to hyperkalemia, but not as a result of the 
disease itself.

Most of the evidence in the literature is based on clinical case 
reports. Various anesthetic techniques have been used in MELAS 
patients without adverse effects.15 In a retrospective review of 
64 patients with mitochondrial disease (6 cases of MELAS), a 
variety of anesthetic techniques were used with no significant 
events such as unanticipated hospital admission, cardiac arrest, 
hypothermia, hyperthermia, prolonged post-anesthesia stay, 
increased lactic acidosis, or metabolic decompensation after 
exposure.15 These techniques included volatile anesthetic gases, 
neuromuscular blockers, and analgesics.15 In yet another case 
series review of patients with mitochondrial cytopathies, all 39 
patients undergoing surgery were anesthetized with inhalational 
gases, local anesthesia, sedation, and general balanced anesthesia 
without any complications, which suggested that the routine 
use of intravenous or inhaled anesthesia did not influence the 
outcome.16

In a pediatric case series review by Footitt et al, 38 patients 
with confirmed mitochondrial disease underwent 69 cases of 
general anesthesia.17 Anesthetic agents included sevoflurane, 
propofol, midazolam, fentanyl, rocuronium, atracurium, alfentanil, 

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Volume 4 - Issue 1 2016 Page 23

and even 2 cases of use of succinylcholine with no adverse events 
noted intraoperatively.17 Three adverse events were reported, none 
in MELAS patients, which included postoperative hypovolemia, 
renal impairment, respiratory failure, and metabolic acidosis.17 
Even though there has been wide documentation of the safety of 
multiple intravenous anesthetics, careful consideration must still 
be taken. 

Although there are no documented cases of adverse effects 
from analgesics in MELAS patients, these patients may be at risk 
for decreased ventilatory response to hypoxia and hypercarbia 
and may suffer respiratory compromise from muscle wasting, 
and thus careful titration of analgesics is necessary.18 Propofol 
has been implicated in propofol infusion syndrome owing to its 
inhibition of free fatty acids entering the mitochondria, impairing 
the electron transport chain, and inhibiting complex II of the 
respiratory chain. Propofol has been used in MELAS patients 
without any adverse side effects, but prolonged infusions can 
mimic MM symptoms such as lactic acidosis.19,20 Use of muscle 
relaxants is also controversial. MELAS has been shown to cause 
focal segmental glomerulosclerosis; thus, it is imperative to take 
into consideration not administering any nephrotoxic agents.21 
The anesthetic plan for the patient in the present case consisted 
of using cisatracurium owing to its elimination via Hoffman 
elimination and ester hydrolysis. There has been one report of 
resistance to cisatracurium in a MELAS patient, but this patient 
received a full intubating dose of cisatracurium with full recovery 
of train-of-four and spontaneous ventilation.22 The effects of 
volatile anesthetics on the mitochondria are debated. They may 
have a protective effect on the mitochondria owing to ischemic 
preconditioning or they may inhibit NADH oxidation.20 

Multiple case reports have also documented the successful 
administration of regional anesthetics in MELAS patients 
without adverse effects, including spinal anesthesia for a 
femur fracture, combined general endotracheal anesthesia 
with epidural anesthesia for gastrectomy, spinal anesthesia for 
appendectomy, epidural anesthesia for postoperative pain control 
after laparotomy, combined general endotracheal anesthesia and 
postoperative epidural anesthesia for colectomy and ovariectomy, 
and epidural catheter placement for labor analgesia.12,19,23-26 It 
is still important for the anesthesia professional to consider 
any neurologic abnormalities of the spinal cord or peripheral 
nerves and to carefully consider coagulation status in this patient 
population. The patient in this case had an unsteady gait and 
normal coagulation studies, but because of his muscle wasting, 
respiratory compromise may have been a possibility if a regional 
anesthetic were chosen and if the level of block was too high. 
Even though the obvious safety of regional anesthesia has been 
confirmed, local anesthetics still affect the mitochondrion. 

This presents another problem that the literature cannot 
answer regarding MELAS patients. Local anesthetics such 
as bupivacaine have been shown to inhibit the mitochondrial 
respiratory chain complex I and cause oxidative phosphorylation 
uncoupling that is potentially detrimental to MELAS patients.27

Upon induction, modified rapid sequence induction with 
cricoid pressure should be instituted in patients with gastric 
involvement such as nausea and vomiting.11 Use of histamine-2 
receptor antagonists and proton pump inhibitors may also 
be helpful to reduce aspiration risk.11 The patient in this case 
did not have any gastrointestinal dysfunction and thus this 
was not performed. A cardiovascularly stable anesthetic is 
best for MELAS patients because aerobic metabolism is 
already dysfunctional in this patient group.11 Intraoperative 
considerations include maintaining normothermia in the 
MELAS patient owing to the impaired mitochondrial chain, 
which is responsible for heat maintenance. This includes 
monitoring temperature through a nasopharyngeal probe and 
warming intravenous fluids and using a forced air warmer.11 
These interventions were used in the anesthetic plan for this 
MELAS patient. Arterial blood gas analysis intraoperatively 
may be appropriate to check glucose and lactate levels. Careful 
titration of muscle relaxants and opiates must be evaluated by 
using a peripheral nerve stimulator and spontaneous ventilation. 
Adequate hydration is paramount. Postoperative considerations 
must include possible metabolic disturbances, postoperative 
respiratory failure, and adequate analgesia to prevent acidosis. 
Other considerations can include adequate control of nausea and 
vomiting and postoperative shivering. These patients should be 
monitored in the intensive care unit because of the potential for 
metabolic disturbances. 

Ideally, clinical trials need to be performed specifically for 
MELAS patients with the same genetic defect and same 
presentation, which would require international collaboration 
to obtain an adequate sample size.28 These trials would need to 
investigate the pharmacology of anesthetic agents as it relates to 
MELAS and other mitochondrial disorders at a similar stage of 
disease progression and similar mitochondrial DNA mutations 
with adequate power, statistically validity, and double-blinded 
randomization.28 Anesthesia professionals could look to national 
consortia such as the North American Mitochondrial Disease 
Consortium to recruit participants for future clinical trials.28 
As more pathophysiologic advances occur in the understanding 
of MMs, anesthetic management will improve.28 Meanwhile, 
each MELAS patient and each patient with MM should be 
treated individually and the anesthetic plan should be adjusted 
accordingly.



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Volume 4 - Issue 1 2016 Page 24

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science.283.5407.1482.
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.3109/07853890.2011.605389.
8.  Codier E, Codier D. Understanding mitochondrial disease and goals for its treatment. Br J Nurs. 2014;23(5):254-260. http://

dx.doi.org/10.12968/bjon.2014.23.5.254.
9.  Online Mendelian Inheritance in Man. http://omim.org/entry/540000. Updated January 2015. Accessed March 8, 2015.
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03-09.
11.  Sasano N, Fujita Y, So MH, Sobue K, Sasano H, Katsuya H. Anesthetic management of a patient with mitochondrial 

myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). J Anesth. 2007;21(1):72-75. http://dx.doi.
org/10.1007/s00540-006-0449-y.

12.  Klingler W, Lehmann-Horn F, Jurkat-Rott K. Complications of anaesthesia in neuromuscular disorders. Neuromuscul Disord. 
2005;15(3):195-206. http://dx.doi.org/10.1016/j.nmd.2004.10.017.

13.  Malignant Hyperthermia Association of the United States. Does mitochondrial myopathy (MM) increase an individual’s 
susceptibility to malignant hyperthermia (MH)? Malignant Hyperthermia Association of the United States website. http://
www.mhaus.org/healthcare-professionals/mhaus-recommendations/mitochondrial-myopathy. Accessed March 8, 2015.

14.  Litman RS. MH-associated diseases: who really needs a non-triggering technique? Semin Anesth. 2007;26(3):113-119. http://
dx.doi.org/10.1053/j.sane.2007.06.007.

15.  Song S, Niezgoda J, Parikh S. Effects of anesthesia in patients with primary mitochondrial disorders. Mitochondrion. 
2013;13(6):908. http://dx.doi.org/10.1016/j.mito.2013.07.029.

16.  Moreira A, Silva A, Antunes M, Neves I, Costa C, Santos P. Anaesthesia in patients with mitochondrial cytopathy: 6 years 
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18.  Thompson VA, Wahr JA. Anesthetic considerations in patients presenting with mitochondrial myopathy, encephalopathy, lactic 
acidosis, and stroke-like episodes (MELAS) syndrome. Anesth Analg. 1997;85:1404-1406.

19.  Maurtua M, Torres A, Ibarra V, Deboer J, Dolak J. Anesthetic management of an obstetric patient with MELAS syndrome: 
case report and literature review. Int J Obstet Anesth. 2008;17(4):370-373. http://dx.doi.org/10.1016/j.ijoa.2007.11.011.

20.  Finsterer J, Segall L. Drugs interfering with mitochondrial disorders. Drug Chem Toxicol. 2010;33(2):138-151. http://dx.doi.
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21.  Park JS, Baek CW, Kang H, et al. Total intravenous anesthesia with propofol and remifentanil in a patient with MELAS 
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22.  Aouad MT, Gerges FJ, Baraka AS. Resistance to cisatracurium in a patient with MELAS syndrome. Paediatr Anaesth. 
2005;15:1124-1127.

23.  Blair MT, Heard G. Neuraxial anesthesia in MELAS syndrome. Anaesth Intensive Care. 2011;39(6):1152-1153.
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mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. Acta Anaesthesiol Sin. 2000;38:107-110.



25.  Bolton P, Peutrell J, Zuberi S, Robinson P. Anaesthesia for an adolescent with mitochondrial encephalomyopathy-
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9592.2003.01001.x.

26.  Gentili ME, Raud C, Enel D, Henot M, Bothereau H. Combination of general anaesthesia and postoperative epidural 
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27.  Nouette-Gaulain K, Jose C, Capdevila X, Rossignol R. From analgesia to myopathy: when local anesthetics impair the 
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2014;171(8):1798-1817. http://dx.doi.org/10.1111/bph.12456.

Summary of Key Points

MELAS is a mitochondrial disorder due to a mutation in mitochondrial DNA that causes a disruption in aerobic metabolism. 
MELAS has varied clinical manifestations including cardiac, neurological, and muscular. Patients may have varied cardiac disturbances 
such as cardiomyopathy, may suffer from strokes, and can also have muscle wasting. 

• The Malignant Hyperthermia Association of the United States does not recommend avoiding volatile agents in 
mitochondrial myopathy patients even though mitochondrial myopathy has a similar presentation of symptoms to malignant 
hyperthermia. 

• The safe use of an anesthetic technique in one type of mitochondrial myopathy does not translate to safety in MELAS. 
However, epidural anesthesia, spinal anesthesia, and general endotracheal anesthesia have all been used safely with various 
muscle relaxants and opioids in patients with MELAS in multiple case reports. 

• It is paramount for the anesthesia provider to remember that the stress of surgery and anesthesia itself can increase metabolic 
demand in these patients who are unable to meet the necessary energy requirements. Therefore, a cardiovascularly stable 
anesthetic is appropriate.

• Avoidance of hypothermia, postoperative nausea vomiting, and lactate in intravenous fluids are mandatory interventions in 
MELAS patients. 

• Careful titration of muscle relaxants, opioids, and other intravenous anesthetics is necessary because these patients are at risk 
for postoperative respiratory failure. 

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