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of Child Neurology

Effect of a Single Dose of Propofol and Lack of Dextrose Administration in a Child With Mitochondrial
Disease: A Case Report
Haifa Mtaweh, Hülya Bayir, Patrick M. Kochanek and Michael J. Bell
J Child Neurol published online 11 September 2013
DOI: 10.1177/0883073813498640
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Brief Communication

Effect of a Single Dose of Propofol and Lack
of Dextrose Administration in a Child With
Mitochondrial Disease: A Case Report

Journal of Child Neurology
00(0) 1-7
ª The Author(s) 2013
Reprints and permission:
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DOI: 10.1177/0883073813498640
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Haifa Mtaweh, MD1,4, Hülya Bayır, MD1,2,4,
Patrick M. Kochanek, MD1,4, and Michael J. Bell, MD1,3,4

Abstract
Propofol infusion syndrome is a recognized complication of prolonged propofol use in the pediatric population, but little is
reported on other metabolic effects of propofol, especially in children with mitochondrial disorders. We report on a child with
metabolic encephalopathy, lactic acidosis, and stroke-like syndrome who received a single dose of propofol for procedural sedation. The patient’s initial presentation was consistent with a mild exacerbation of her underlying disease. She received a single dose
of propofol and non–dextrose-containing fluids during a magnetic resonance imaging (MRI) study to rule out stroke and
progressed to develop severe acidosis, neurologic deterioration, and cardiorespiratory compromise. This is the first case report
of severe metabolic disturbances after a single dose of propofol administered for procedural sedation in a patient with metabolic
encephalopathy, lactic acidosis, and stroke-like syndrome and it questions the safety of propofol and absence of dextrose infusions
during an acute illness in patients with mitochondrial disorders.
Keywords
propofol, metabolic encephalopathy, lactic acidosis, MELAS, mitochondrial disorders
Received April 04, 2013. Received revised April 28, 2013. Accepted for publication July 01, 2013.

Several reports in the literature emphasize that prolonged exposure to propofol can cause life-threatening metabolic disturbances in relatively healthy children, ultimately leading to the
description of propofol infusion syndrome by Bray in 1998.1,2
The US Food and Drug Administration (FDA) defines propofol
infusion syndrome as unexplained metabolic acidosis with or
without rhabdomyolysis with progressive myocardial dysfunction after exposure to propofol.2 They issued a recommendation
in 2001 to avoid prolonged sedation with propofol in children.3
Despite these reports of side effects and the presumption
that propofol toxicity appears to be related to alterations in cellular metabolism, little is known about propofol’s effects in
children with mitochondrial disorders. There are reports from
Japan and Korea detailing adult patients with mitochondrial
disorders who underwent propofol induction and general
anesthesia without suffering sequelae.4-8 We present a case
of a child with a known metabolic disorder who suffered a significant worsening of her metabolic disorder shortly after
receiving a single dose of propofol for procedural sedation.

Case
A 16-year-old Amish girl was diagnosed with metabolic encephalopathy, lactic acidosis and stroke-like syndrome approximately

1 year prior to the current admission when she presented to our
institution after an episode of status epilepticus. The diagnosis
of metabolic encephalopathy, lactic acidosis and stroke-like
syndrome was confirmed by a positive 6-point mutation (3243
A>G) in the tRNALeu(UUR) gene on chromosome analysis of
blood. Over the intervening time period, she was treated with
coenzyme Q and carnitine for her mitochondrial disorder and
levetiracetam as a therapy for her seizures that are of generalized
tonic clonic nature. For her current admission, she complained of
a 1-day history of decreased vision in the right eye, dizziness,

1

Department of Critical Care Medicine, University of Pittsburgh School of
Medicine, Pittsburgh, PA, USA
2
Department of Environmental and Occupational Health, University of
Pittsburgh School of Medicine, Pittsburgh, PA, USA
3
Department of Neurological Surgery, University of Pittsburgh School of
Medicine, Pittsburgh, PA, USA
4
Safar Center for Resuscitation Research, University of Pittsburgh School of
Medicine, Pittsburgh, PA, USA
Corresponding Author:
Michael J. Bell, MD, Critical Care Medicine, Neurological Surgery and
Pediatrics, Safar Center for Resuscitation Research, 3434 Fifth Avenue,
Pittsburgh, PA 15260, USA.
Email: bellmj4@upmc.edu

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Journal of Child Neurology 00(0)

Table 1. Description of Acid/Base Balance of Patient.a
Day
Time
pH
PCO2 (mmHg)
HCO3 (mmol/L)
Base deficit (mmol/L)
Lactate (mmol/L)

Admission (Day 1)

Day 1

Day 1

Day 2

Day 3

Day 4

12:00
7.30 (v)
46
23
4
6.7

18:25
6.83 (c)
42
7
27

20:38
7.07 (a)
33
10
19
11.2

20:18
7.26 (a)
38
17
10
7.3

20:04
7.35 (a)
35
20
5
5.5

20:12
7.42 (a)
35
23
1
5.4

Abbreviations: a, arterial; c, capillary; v, venous.
a
Propofol administration occurred at 14:00 on day 1 of admission. Gas at 18:25 was drawn 10 min prior to the seizure episode.

Figure 1. Glucose infusion rate on the day of admission. Patient received no glucose for the duration of the magnetic resonance imaging (MRI).
Glucose-containing fluids were started on pediatric intensive care unit admission.

severe headache, and vomiting. Past medical history was significant for a minor fall at her home several days prior to admission
for which she denied any loss of consciousness and had returned
to her normal functioning. Physical examination in the
Emergency Department demonstrated an awake, alert patient
with normal pupillary exam but no light tracking. She was able
to move all extremities, but detailed examination was limited
because of lack of cooperation, with the rest of the physical examination being noncontributory. Initial laboratory evaluation
demonstrated normal electrolytes, normal glucose level of 138
mg/dL, and normal serum levels of liver enzymes (see Table 1).
A venous blood gas demonstrated a mild, metabolic acidosis

(pH of 7.30, PCO2 of 46, HCO3 of 23, base deficit of 4) and a
lactate level of 6.7 mmol/L (baseline lactate level for this patient
is *4 mmol/L), consistent with her diagnosis of metabolic encephalopathy, lactic acidosis and stroke-like syndrome. She underwent emergent computed tomography (CT) of the brain to
determine if her symptoms were due to an evolving stroke or
sequelae from her previously described fall, but this demonstrated
no evidence of acute trauma, no extra-axial fluid/blood collections, and no evidence of stroke. Because an early ischemic stroke
could not be excluded from this study, a brain magnetic resonance
imaging (MRI) was performed that ruled out an acute infarct or
perfusion defect. There was improvement of the baseline T2

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Figure 2. Systolic blood pressure on the day of admission. Patient had a decrease in her blood pressure after propofol was administered but
that was not sustained.

prolongation in the bilateral temporal occipital lobes. Magnetic
resonance spectroscopy demonstrated newly elevated lactate
peaks markedly in the occipital lobes.
Sedation for the MRI consisted of intravenous administration of 1.25 mg/kg of propofol and inhalation of sevoflurane
(1.8%-2.5%) with an airway secured via a laryngeal mask
airway. The procedure lasted approximately 2 hours, during
which she received no dextrose-containing fluids, but she was
given a total of 12 mL/kg of normal saline (see Figure 1 for
glucose infusion rate). Systolic blood pressure and arterial
hemoglobin oxygen saturation were stable (Figures 2 and 3)
during the procedure and she was brought to the pediatric intensive care unit for further management of her condition. On
arrival to the pediatric intensive care unit, her Glasgow Coma
Scale score was 10 and she suffered a 10-minute-long generalized tonic-clonic seizure. Serum glucose, sodium, and calcium
at this time were within normal limits. She was treated with
benzodiazepines and a bolus dose of intravenous fosphenytoin
(20 mg/kg). She developed respiratory failure and was tracheally
intubated using fentanyl (1.2 mg/kg, intravenous) and rocuronium (1.5 mg/kg, intravenous). No desaturations or hypotension
were noted during this stage. After placement of arterial and central venous catheters, laboratory analysis demonstrated severe
metabolic acidosis and increases in serum lactate (arterial blood
gas: pH of 7.07, PCO2 of 33, HCO3 of 10, base deficit of 19,

serum lactate of 11.2 mmol/L). An electroencephalogram (EEG)
was performed that demonstrated near continuous right-sided
discharges in the occipital region with spreading of the ictal
focus throughout the right hemisphere and the left posterior leads
(Figures 4 and 5). This pattern persisted for 2 hours despite
administration of multiple anticonvulsants (a total of 30 mg/kg
fosphenytoin, 20 mg/kg of phenobarbital, and 40 mg/kg of levetiracetam intravenous, and a continuous intravenous midazolam
infusion titrated to a dose of 0.3 mg/kg/h). After several hours of
resuscitation with isotonic saline solutions, she continued to
have hemodynamic instability and required inotropic support.
The patient did not demonstrate arrhythmias during her pediatric
intensive care unit stay and hemodynamic instability was
attributed to the cardiac depressant effects of the antiepileptic
medication. The patient was able to wean off all inotropic support after the midazolam infusion was tapered down.
During the pediatric intensive care unit stay, the patient’s
severe acidosis was treated with repeated doses of sodium
bicarbonate, ultimately requiring addition of bicarbonate to her
maintenance fluids. To treat her metabolic response, she was
started on high dextrose (20%)-containing solutions and transitioned to lower concentrations after several days. In addition,
the patient’s metabolic encephalopathy, lactic acidosis and
stroke-like syndrome was managed with pyridoxine, levocarnitine, coenzyme Q, and an arginine infusion of 0.6 g/kg/d after a

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Journal of Child Neurology 00(0)

Figure 3. Arterial hemoglobin oxygen saturation on the day of admission. Patient maintained normal arterial hemoglobin oxygen saturation
during her first day of admission.

bolus of 0.6 g/kg. On discharge from our institution, the child
had regained her previous level of functioning, with return of
baseline vision and well-controlled seizures with phenobarbital.

Discussion
The syndrome of metabolic encephalopathy, lactic acidosis, and
stroke-like syndrome was first described in 1984.9 It is characterized by encephalopathy presenting as dementia or seizures,
stroke-like episodes before 40 years of age, and evidence of mitochondrial dysfunction such as lactic acidosis, ragged red fibers, or
both. Lactic acidosis was the most consistent lab abnormality in
the series of patients reported by Hirano and colleagues.10 In this
case, the patient had a metabolic encephalopathy, lactic acidosis
and stroke-like syndrome exacerbation and presented with a rule
out stroke in evolution picture, and only a very mild metabolic
acidosis that was markedly and acutely worsened after propofol
administration and lack of dextrose-containing fluids infusion
during her procedure.
Propofol is now commonly used as an anesthetic or an adjuvant in adults and children, yet its precise mechanism of action is
relatively unclear. As an anesthetic, it is unrelated to any of the
other major classes of analgesics (opioids), anxiolytics (benzodiazepines), or anesthetics (barbiturates, inhalational agents,
ketamine among others). As a part of its side-effect profile,

propofol is thought to inhibit beta-oxidation of free fatty acids
and the mitochondrial electron transport chain, leading to disruption in adenosine triphosphate production, cellular hypoxia, and
buildup of toxic fatty acid intermediates.2 It has been speculated
that the lipid component of the formulation could play a role in
its toxicity for patients with fatty acid oxidation defects.11 Wolf
and colleagues have suggested that the insufficient caloric intake
that can occur in the early stages of critically ill children with
metabolic disorders could cause such children to use fats as a primary energy source because of their limited glycogen reserves.
With this assumption, an intact fatty acid oxidation axis within
the mitochondria would be more critical and can put children
with such disorders at risk for adverse effects of drugs such as
propofol. Indirect evidence of such an effect can be that propofol
infusion syndrome in healthy children appears to mimic some
aspects of the clinical syndromes exhibited in children with
mitochondrial myopathies.12 In our case, the child did not appear
to fulfill the published criteria for propofol infusion syndrome
(lack of evidence of discolored urine and not exhibiting severe
bradycardia). However, we propose that her deterioration after
receiving propofol might reflect an adverse side effect from drug
administration that was also worsened by the lack of dextrose
administration because she developed a severe acidosis after the
MRI. We believe that in the face of an acute presentation of a
metabolic encephalopathy, lactic acidosis, and stroke-like

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Figure 4. Electroencephalogram at time of seizures. Electroencephalography (EEG) demonstrated right-sided discharges in the occipital region.
This EEG recording was obtained while the patient was being treated with a midazolam infusion.

syndrome exacerbation, administration of propofol worsened her
deterioration given the drug’s effects on the mitochondria. It is
noteworthy that the acidosis emerged after a single dose—suggesting markedly enhanced sensitivity to propofol toxicity in this
child, particularly since it is generally observed with continuous
infusion. In addition, patients with metabolic encephalopathy,
lactic acidosis, and stroke-like syndrome have a high glycolytic
rate, increased lactate production, reduced glucose oxidation,
and markedly reduced adenosine triphosphate production.
Therefore, the lack of dextrose administration coupled with
propofol might have led to this acute severe worsening metabolic crisis.13
In contrast to our findings, there are several reports in the
literature that suggest the use of propofol in children with mitochondrial disease can be safe. Cheam and colleagues reported a
case of a 6-year-old girl with complex I respiratory chain
enzyme deficiency undergoing a hip surgery who was induced
with propofol of 3.3 mg/kg and maintained with an infusion at
13-17 mg/kg/h. Lactate levels were stable during and after the
procedure in this case.14 Gurrieri and colleagues reported a case
series of 9 patients with metabolic encephalopathy, lactic
acidosis and stroke-like syndrome between September 1997 and
October 2010 at Mayo Clinic. This cohort underwent 20 general
anesthetic procedures, 12 of them prior to metabolic encephalopathy, lactic acidosis and stroke-like syndrome diagnosis. Propofol
was administered in 17 cases without any sign of deterioration in
their clinical status.15 Bolton and colleagues presented a 17-yearold patient with metabolic encephalopathy, lactic acidosis and

stroke-like syndrome who presented for fundoplication and
insertion of feeding tube. Twenty percent glucose was infused
preoperatively and postoperatively to prevent catabolism.
Anesthesia was induced with propofol and the child was maintained with a propofol infusion throughout the case, with no
changes in lactate concentrations.16 The major differences
between these cases and ours is that our patient was not being
anesthetized in a stable baseline state for an elective procedure;
rather she was acutely ill and was being sedated for an emergency
diagnostic procedure in the setting of a mild ongoing metabolic
derangement. This difference could be quite important. For example, our patient had been vomiting and, unlike some of the aforementioned cases, did not receive glucose loading prior to propofol
administration. This suggests the possibility that propofol has risk
in the setting of metabolic encephalopathy, lactic acidosis and
stroke-like syndrome during an acute presentation and/or when
a mild metabolic acidosis is already present.
There are no published guidelines for sedating patients with
mitochondrial disease, but some articles have published
recommendations on what to use or avoid in these cases. Some
authors emphasize maintaining normoglycemia, normothermia,
hemodynamic stability, and avoiding hypoxia so as not to stress
the diseased mitochondria.11,17 As for medication choice, inhalation induction has been recommended by some to avoid the possible sensitivity of this patient population to other agents.17-19
Regarding fluid choice in this particular patient population,
dextrose-containing fluids are a must to prevent further exacerbation of the metabolic crisis and to avoid a catabolic state.13,20

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Journal of Child Neurology 00(0)

Figure 5. Electroencephalogram after resolution of seizures. Electroencephalography (EEG) demonstrated diffuse bihemispheric delta waves
but no electrographical seizures. This EEG was obtained when the patient was medicated with phenobarbital.

As for our patient, it is possible that her metabolic deterioration
had occurred without administration of propofol. Given the
relatively sporadic nature of reports on propofol in the setting
of mitochondrial disease and the potentially devastating consequences of triggering metabolic crisis and/or neurologic complications in these patients, we believe that clinicians caring for
children with metabolic disorders should optimize their clinical
status by providing dextrose-containing infusions, maintaining
normothermia and hemodynamic stability, monitoring for signs
of metabolic deterioration by following their acid-base balance,
and finally consider potential side effects of propofol when
administering anesthetics for diagnostic or therapeutic procedures during acute presentations that include some degree of a
metabolic acidosis or require critical care.
Acknowledgments
Mr Russell Phillips, lead EEG technologist in Department of Neurology at Children’s Hospital of Pittsburgh.

Author Contributions
HM cared for the patient and wrote the manuscript. HB cared for the
patient and provided mentorship for writing the manuscript. PMK
provided mentorship for writing the manuscript. MJB cared for the
patient and provided mentorship for writing the manuscript.

Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.

Funding
The authors received no financial support for the research, authorship,
and/or publication of this article.

Ethical Approval
Because of the nature of this report, no institutional review board
approval was obtained. All patient identifiers have been removed from
the document and figures.

References
1. Bray RJ. Propofol infusion syndrome in children. Paediatr
Anaesth. 1998;8:491-499.
2. Wong JM. Propofol infusion syndrome. Am J Therap. 2010;17:
487-491.
3. Dear healthcare provider letter. Newark, DE: Astra Zeneca.
March 26, 2001.
4. Sasano N, Fujita Y, So M, et al. Anesthetic management of a
patient with mitochondrial myopathy, encephalopathy, lactic
acidosis, and stroke-like episodes (MELAS) during laparotomy.
J Anesth. 2007;21:72-75.
5. Imai Y, Kitamura T, Kawamura G, et al. Anesthetic management
of emergency total gastrectomy in a patient with mitochondrial
encephalomyopathy: a case of gastric perforation accompanied
by systemic inflammatory response syndrome [in Japanese].
Masui. 2010;59:765-769.

Downloaded from jcn.sagepub.com at St Petersburg State University on December 30, 2013

Mtaweh et al

7

6. Tatsumi Y, Nakashima M, Kitao T, et al. Anesthetic management
of a patient with mitochondrial encephalomyopathy under total
intravenous anesthesia [in Japanese]. Masui. 2006;55:1228-1230.
7. Shibukawa K, Kawamata M, Seki S, et al. The use of propofol
combined with nitrous oxide and fentanyl in anesthetic management of a patient with mitochondrial encephalomyopathy
[in Japanese]. Masui 2002;51:888-891.
8. Park JS, Baek CW, Kang H, et al. Total intravenous anesthesia
with propofol and remifentanil in a patient with MELAS syndrome—a case report. Korean J Anesthesiol. 2010;58:409-412.
9. Pavlakis SG, Phillips PC, DiMauro S, et al. Mitochondrial
myopathy, encephalopathy, lactic acidosis, and strokelike episodes:
a distinctive clinical syndrome. Ann Neurol. 1984;16:481-488.
10. Hirano M, Pavlakis SG. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS): current
concepts. J Child Neurol. 1994;9:4-13.
11. Farag E, Deboer G, Cohen BH, Niezgoda J. Metabolic acidosis
due to propofol infusion. Anesthesiology. 2005;102:697-698;
author reply 698-699.
12. Wolf A, Weir P, Segar P, et al. Impaired fatty acid oxidation in
propofol infusion syndrome. Lancet. 2001;357:606-607.

13. Koga Y, Povalko N, Nishioka J, et al. MELAS and L-arginine
therapy: pathophysiology of stroke-like episodes. Ann N Y Acad
Sci. 2010;1201:104-110.
14. Cheam EW, Critchley LA. Anesthesia for a child with complex I
respiratory chain enzyme deficiency. J Clin Anesthe. 1998;10:
524-527.
15. Gurrieri C, Kivela JE, Bojanic K, et al. Anesthetic considerations in
mitochondrial encephalomyopathy, lactic acidosis, and stroke-like
episodes syndrome: a case series. Can J Anaesth. 2011;58:751-763.
16. Bolton P, Peutrell J, Zuberi S, Robinson P. Anaesthesia for an adolescent with mitochondrial encephalomyopathy-lactic acidosisstroke-like episodes syndrome. Paediatr Anaesth. 2003;13:453-456.
17. Burns AM, Shelly MP. Anaesthesia for patients with mitochondrial myopathy. Anaesthesia. 1989;44:975-977.
18. Lauwers MH, Van Lersberghe C, Camu F. Inhalation anaesthesia
and the Kearns-Sayre syndrome. Anaesthesia. 1994;49:876-878.
19. Wallace JJ, Perndt H, Skinner M. Anaesthesia and mitochondrial
disease. Paediatr Anaesth. 1998;8:249-254.
20. Santa KM. Treatment options for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)
syndrome. Pharmacotherapy. 2010;30:1179-1196.

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