Society for Pediatric Anesthesia

Section Editor: Peter J. Davis

Malignant Hyperthermia in Children: An Analysis of

the North American Malignant Hyperthermia Registry
Priscilla Nelson, MD, and Ronald S. Litman, DO

BACKGROUND: Clinical characteristics of malignant hyperthermia (MH) in pediatric patients

have not been elucidated. In this study, we used the North American Malignant Hyperthermia
Registry to determine differences in clinical characteristics of acute MH across pediatric age
groups. We hypothesized that there are differences in clinical presentation, clinical course, and
outcomes, which correlate with age. A secondary aim was to determine the types of preexisting
medical conditions associated with pediatric MH.
METHODS: We performed a retrospective review of the North American Malignant Hyperthermia
Registry to identify pediatric subjects (up to and including 18 years) with an MH clinical grading
score at or above 35 indicating very likely or almost certain MH. Preoperative patient char-
acteristics, perianesthetic factors, and outcome data were compared for 3 cohorts based on
age: 0 to 24 months, 25 months to 12 years, and 13 to 18 years. We used statistical analysis
to determine differences among the groups.
RESULTS: We analyzed 264 records: 35 in the youngest age group, 163 in the middle age group,
and 66 in the oldest group. There was no indication of any predisposing risk factors for MH based
on family history or physical examination. Sinus tachycardia, hypercarbia, and rapid temperature
increase were the most common signs of acute MH (observed in 73.1%, 68.6%, and 48.5%,
respectively) and were more common in the oldest age cohort. Higher maximum temperatures
and higher peak potassium values were seen in the oldest age cohort. Masseter spasm was more
common in the middle age cohort. The youngest age cohort was more likely to develop skin mot-
tling and was approximately half as likely to develop muscle rigidity. The youngest age group also
demonstrated significantly higher peak lactic acid levels and lower peak creatine kinase values.
Treatments were similar across age cohorts. There were 10 MH-associated deaths, 6 in the mid-
dle age group and 4 in the oldest age group. Recrudescence of symptoms after initial treatment
occurred in 14.4% of subjects, with no difference across age cohorts. Two of these subjects, 1 in
the middle age group and 1 in the oldest age group, died after the recrudescence event.
CONCLUSIONS: There are differences in clinical characteristics of acute MH among different
age cohorts in childhood. Older subjects demonstrated higher body temperatures and higher
potassium levels, and the youngest subjects had greater levels of metabolic acidosis. Most
children in each age group were phenotypically normal before developing MH. (Anesth Analg
2014;118:36974)

A
pproximately 17% of cases of malignant hyperther-
mia (MH) occur in children,1 yet the clinical charac-
teristics of MH in the pediatric population have not
been fully elucidated. Gaps in knowledge include preopera-
tive risk stratification as well as clinical presentations and
responses to treatment that are unique to children based on
developmental age.
From the Department of Anesthesiology and Critical Care, The Childrens
Hospital of Philadelphia, Perelman School of Medicine at the University of
Pennsylvania, Philadelphia, Pennsylvania.
Accepted for publication August 7, 2013.
Funding: Departmental sources only: Childrens Anesthesia Associates.
The authors declare no conflicts of interest.
This report was previously presented, in part, at the Annual meeting of the
American Society of Anesthesiologists, Washington, DC, October 2012.
Supplemental digital content is available for this article. Direct URL citations
appear in the printed text and are provided in the HTML and PDF versions of
this article on the journal's Web site (www.anesthesia-analgesia.org).
Reprints will not be available from the authors.
Address correspondence to Ronald S. Litman, DO, Department of Anesthesiol-
ogy and Critical Care, The Childrens Hospital of Philadelphia, 34th St., Civic
Center Blvd, Philadelphia, PA 19104. Address e-mail to litmanr@email.chop.edu.
Copyright 2013 International Anesthesia Research Society
DOI: 10.1213/ANE.0b013e3182a8fad0
The primary aim of this study was to use data from
the North American Malignant Hyperthermia Registry
(NAMHR)2,3 to determine the differences in clinical char-
acteristics of acute MH across pediatric age populations.
Given the developmental changes in body structure and
composition throughout childhood, we hypothesized
that there are differences in clinical presentation, clini-
cal course, and outcomes based on the age group of the
patient. A secondary aim was to determine the types of
preexisting medical conditions that were associated with
pediatric MH cases.
METHODS
We obtained permission from the IRB of the Stokes Research
Institute of The Childrens Hospital of Philadelphia (require-
ment for written consent was waived by the IRB because
the database was de-identified at its source) to conduct a
retrospective analysis of all subjects up to and including 18
years of age in the NAMHR with an MH clinical grading
scale (CGS) score at or above 35, indicating very likely
or almost certain MH. The CGS represents a qualitative
score of the likelihood that an MH event occurred, on the
basis of clinical characteristics and laboratory results.4

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Malignant Hyperthermia in Children
The NAMHR database is divided into 3 general catego-
ries of data that correspond to the data fields of the Adverse
Metabolic or Muscular Reaction to Anesthesia (AMRA)
Report (Appendix, see Supplemental Digital Content 1,
http://links.lww.com/AA/A601): (1) preoperative patient
demographics and risk factors; (2) clinical characteristics of
the acute MH event; and (3) postevent clinical characteris-
tics and outcomes. The database was supplied to us in an
Excel spreadsheet format (Microsoft, Redwood, WA).
Statistical Analyses
To test our hypotheses, we divided eligible subjects into 3 age-
based cohorts: 0 to 24 months (youngest age group), 25 months
to 12 years (middle age group), and 13 to 18 years (oldest
age group). Comparisons of variables of interest among age
cohorts were performed with Stata IC 10.1 (College Station,
TX), using the Kruskal-Wallis test to analyze continuous vari-
ables and 2 or Fisher exact test to compare categorical vari-
ables. Statistical significance was defined as P < 0.05.
RESULTS
There were 351 subjects aged 18 years and younger in the
NAMHR, stemming from events that occurred between 1960
and 2011. When these records were subjected to a screen
based on the MH CGS score, we obtained 264 (75.2%) records
that met the criteria for MH as very likely or almost cer-
tain. Of these, 35 belonged to the youngest age group, 163 in
the middle age group, and 66 in the oldest age group.
Preoperative Patient Demographics and Risk
Factors
Most subjects in our cohort were male; although this pre-
dominance held across age cohorts, it was more pronounced
in the oldest age group (P = 0.04) (Table 1). Most subjects
were Caucasian; no significant differences were noted in
racial composition among age groups. Although the young-
est cohort trended towards a higher family history of MH
(P=0.09), there appeared to be no differences between the
age groups with regard to family history of MH-related
events or illnesses. Forty-nine subjects (18.5%) had a family
history of MH or other MH-related illness, but this did not
significantly differ by age group. The youngest age group
trended toward being more likely to have generalized mus-
cle weakness (P=0.07) and was noted to have a higher inci-
dence of undescended testes (P=0.04) and inguinal hernia
(P=0.04). These differences are likely related to a surgical
case-based bias. No difference was noted in the number of
prior anesthetic procedures, but the MH event was the first
procedure for 50% of patients and the second procedure for
20% (not shown in Table1).
The case type by service was distributed across special-
ties, with cases most commonly involving ear, nose, and
throat (29%) and orthopedics (21.2%). The type of case was
variable by age group, with urological cases accounting for
nearly 30% of the youngest group events (P 0.001), ear-
nose-throat cases accounting for nearly 40% of the middle
group events (P 0.001), and orthopedic cases accounting
for 50% of oldest cohort events (P 0.001). Cases for the
youngest group were nearly all scheduled, while the adoles-
cent cohort had a higher percentage of emergent procedures
370
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(P 0.001). Although denominators for non-MH cases are
not available, these case distributions are likely reflective of
a typical case distribution in children by age group.
Most children had induction of general anesthesia with
IV drugs, although the youngest group was more likely
to receive an inhaled induction (P=0.003). As expected, IV
induction was significantly associated with emergent cases
(97.4% vs 80.9%, P=0.009). The youngest age group was less
likely to receive IV succinylcholine (P 0.001), vecuronium
(P=0.001), propofol (P 0.001), or fentanyl (P < 0.001) but was
more likely to receive halothane (P < 0.001) or sevoflurane
(P = 0.013) compared with the older cohorts. These results
are also likely explained by normal age-based clinical practice.
Event Characteristics
Sinus tachycardia, hypercarbia, and rapid temperature
increase were the most commonly observed physical exam-
ination findings (observed in 73.1%, 68.6%, and 48.5%,
respectively) (Table2); the oldest cohort was more likely to
develop these findings. The oldest age group took longer
to reach their maximum end-tidal CO2 value, had higher
peak potassium values, and was more likely to demonstrate
sweating during the event. The middle age cohort had a
lower maximum end-tidal CO2 and blood gas Pco2 com-
pared with the youngest and oldest age groups. The middle
age cohort was more likely to develop masseter spasm, and
the youngest age cohort was more likely to develop skin
mottling. Although no significant differences were noted in
the incidence of generalized muscle rigidity, dark colored
urine, tachypnea, cyanosis, ventricular arrhythmias, or
overall temperature increase among age groups, the young-
est age cohort was approximately half as likely to demon-
strate muscle rigidity.
Masseter spasm was significantly more common in chil-
dren who received succinylcholine (75/125 vs 11/128, P <
0.001). However, there were differences when analyzed sep-
arately by age group. For example, although infrequently
used in subjects in the youngest age group, masseter spasm
and subsequent MH occurred in 4 of the 5 subjects in this
age group who received succinylcholine. In the oldest age
group, there was no significant difference in appearance of
masseter spasm between the subjects who did and did not
receive succinylcholine (P= 0.17).
Subjects in the oldest age cohort reached a higher maxi-
mum temperature compared with those in the youngest and
middle cohorts; subjects in the youngest age group tended
to take longer to reach their maximum value (P= 0.07), and
they tended to have a lower blood pH (P= 0.06). Subjects
in the youngest age group also demonstrated significantly
higher peak lactic acid levels (P= 0.0025) and lower peak
creatine kinase (P 0.001) values.
Treatments and Outcomes
For nearly all treatments, regimens were similar across age
cohorts. The oldest age cohort was more likely to receive
active cooling (they had higher temperatures) and fluid
administration (Table3). The older cohort more commonly
received glucose and insulin in their treatment, which likely
related to their higher potassium values. Dantrolene was
administered in >73% of events, with the average initial and
anesthesia & analgesia
Table 1.Patient Demographics and Procedural Characteristics
Youngest Middle Oldest
(n = 35) (n = 163) (n = 66)
Characteristic n % n % n % P
Male 26 74.3 108 66.3 55 83.3 0.04
Female 9 25.7 54 33.1 11 16.7
Race
Caucasian 22 62.9 119 73.0 44 66.7 0.19
Hispanic 8 22.9 16 9.8 5 7.6
African American 0 0.0 1 0.6 2 3.0
Native American 3 8.6 14 8.6 12 18.2
Hawaiian/Pacific islander 1 2.9 2 1.2 0 0.0
African 0 0.0 0 0.0 1 1.5
East Asian 0 0.0 2 1.2 0 0.0
South Asian 0 0.0 3 1.8 2 3.0
Middle Eastern 0 0.0 2 1.2 0 0.0
Other race not listed 1 2.9 4 2.5 0 0.0
Family history
Malignant hyperthermia 4 11.4 5 3.1 4 6.1 0.09
Masseter rigidity 0 0.0 0 0.0 1 1.5 0.38
Intraoperative event 1 2.9 5 3.1 2 3.0 1
Sudden infant death syndrome 2 5.7 4 2.5 2 3.0 0.51
Sudden death 0 0.0 1 0.6 3 4.5 0.1
Heat stroke 1 2.9 3 1.8 4 6.1 0.19
Heat intolerance 0 0.0 1 0.6 1 1.5 0.62
Myopathy 1 2.9 9 5.5 3 4.5 1
Any family history (from the above) 9 25.7 26 16.0 14 21.2 0.33
Physical exam findings
Increased muscle tone 1 2.9 6 3.7 1 1.5 0.87
Decreased muscle tone 3 8.6 9 5.5 0 0.0 0.05
General muscle weakness 3 8.6 3 1.8 1 1.5 0.07
Myopathy 0 0.0 6 3.7 0 0.0 0.26
Ptosis 0 0.0 7 4.3 2 3.0 0.63
Strabismus 1 2.9 10 6.1 2 3.0 0.64
Hiatal hernia 0 0.0 2 1.2 0 0.0 1
Inguinal hernia 5 14.3 9 5.5 1 1.5 0.04
Umbilical hernia 0 0.0 2 1.2 0 0.0 1
Undescended testicles 3 8.6 3 1.8 0 0.0 0.04
Clubbed foot 1 2.9 6 3.7 3 4.5 0.9
Joint hypermobility 0 0.0 0 0.0 2 3.0 0.08
Kyphoscoliosis 0 0.0 4 2.5 1 1.5 1
Winged scapulae 0 0.0 3 1.8 0 0.0 0.71
Skeletal fractures 0 0.0 2 1.2 1 1.5 1
Case type
Cardiothoracic 2 5.7 2 1.2 0 0.0 0.14
Dental 1 2.9 22 13.5 0 0.0 0.001
Ear, nose, and throat 8 22.9 63 38.7 6 9.1 <0.001
Ophthalmology 1 2.9 7 4.3 3 4.5 1
General surgery 7 20.0 11 6.7 9 13.6 0.02
Gynecology 0 0.0 0 0.0 1 1.5 0.38
Neurosurgery 1 2.9 4 2.5 1 1.5 1
Oral surgery 0 0.0 4 2.5 4 6.1 0.3
Orthopedic 2 5.7 21 12.9 33 50.0 <0.001
Plastic surgery 2 5.7 9 5.5 4 6.1 1
Radiology 1 2.9 0 0.0 0 0.0 0.13
Urology 10 28.6 10 6.1 2 3.0 <0.001
Procedure timing
Elective 34 97.1 144 88.3 39 59.1 <0.001
Emergent 1 2.9 16 9.8 26 39.4
Unknown 0 0.0 3 1.8 1 1.5
Anesthesia induction method
Intravenous 23 65.7 136 83.4 62 93.9 0.003
Inhaled 12 34.3 24 14.7 3 4.5
Other 0 0.0 1 0.6 0 0.0
Unknown 0 0.0 2 1.2 1 1.5

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Malignant Hyperthermia in Children

Table 2.Physical Findings and Laboratory Values

Youngest Middle Oldest
Characteristic, N (n = 35) (n = 163) (n = 66)
Physical exam findings n % n % n % P
Elevated temperature 21 60.0 71 43.6 36 54.5 0.1
Rapidly increasing temperature 13 37.1 51 31.3 44 66.7 <0.001
Sweating 0 0.0 11 6.7 17 25.8 <0.001
Masseter spasm 5 14.3 74 45.4 7 10.6 <0.001
Generalized muscular rigidity 6 17.1 53 32.5 25 37.9 0.96
Dark urine 2 5.7 24 14.7 6 9.1 0.26
Tachypnea 12 34.3 43 26.4 21 31.8 0.52
Hypercarbia 27 77.1 95 58.3 59 89.4 <0.001
Cyanosis 2 5.7 16 9.8 7 10.6 0.75
Skin mottling 5 14.3 8 4.9 7 10.6 0.07
Sinus tachycardia 26 74.3 110 67.5 57 86.4 0.01
Ventricular tachycardia 2 5.7 9 5.5 3 4.5 1
Ventricular fibrillation 0 0.0 5 3.1 4 6.1 0.27
Vital sign and laboratory data Mean SD Mean SD Mean SD P
Maximum temperature (C) 38.4 (1.4) 38.2 (1.7) 40.2 (8.3) 0.0006
Time to maximum temperature (minutes) 181.7 (282.3) 137.1 (191.3) 146.9 (183.0) 0.07
Maximum end-tidal CO 2a (mm Hg) 75.9 (23.0) 62.8 (23.9) 75.2 (16.8) 0.0001
Time to maximum etCO2 (min) 640.8 (205.6) 682.1 (228.9) 861.7 (329.7) 0.0001
Time to first blood gas (min) 183.6 (253.5) 151.2 (219.3) 176.2 (212.3) 0.18
Fio2 0.75 (0.35) 0.78 (0.32) 0.82 (0.28) 0.51
pH 7.16 (0.19) 7.23 (0.14) 7.2 (0.13) 0.06
Pco2 (mm Hg) 65.3 (39.4) 53.2 (24.1) 61.6 (18.9) 0.0008
Po2 (mm Hg) 157.6 (142.4) 236.5 (176.1) 275.5 (162.2) 0.002
Base excess (mEq/L) 6.6 (5.4) 5.6 (6.2) 4.9 (5.7) 0.19
Bicarbonate (mEq/L) 21.69 (4.58) 21.34 (4.91) 22.75 (3.98) 0.052
Peak lactic acid (mmol/L) 5.2 (5.8) 1.7 (3.4) 3.8 (2.3) 0.003
Peak potassium (mEq/L) 5.07 (1.30) 5 (1.68) 5.44 (1.24) 0.004
Peak creatinine kinase (U/L) 17843.5 (58940.6) 32895.8 (70279.5) 20527.8 (61000.7) 0.0001
a
etCO2 = end-tidal carbon dioxide.

total doses being 2.4 mg/kg and 5.9 mg/kg, respectively.
These doses were similar across groups. Overall, 21.6% of
patients reported side effects after dantrolene administra-
tion, the most common of which was muscle weakness,
which was more commonly reported in the oldest age
cohort (the youngest group would not have been able to
report such an effect).
There were 10 MH-associated deaths in the entire cohort.
Six of these deaths occurred in the middle age group (3.7%),
and 4 occurred in the oldest age group (6.1%). Five of these
patients (50%) received dantrolene during the course of
their treatment. In examining these cases further, the deaths
occurred between 1990 and 2010. Factors associated with
death, such as drugs, are impossible to determine because
of the way knowledge of MH and its treatments changed
over time. Other major complications were uncommon,
with cardiac dysfunction having the highest incidence at
4.5%. Such events tended to be more common in the oldest
age group (P= 0.06).
Recrudescence of symptoms after initial treatment
occurred in 14.4% of cases, with no difference across age
cohorts. Two of these cases were fatal despite treatment
with dantrolene: one in the middle age group (4-year-old,
recrudesced 6 hours after the initial event), and 1 in the old-
est age group (14-year-old, recrudesced 24 hours after the
initial event).
DISCUSSION
In this retrospective analysis of pediatric MH cases reported
to the NAMHR, we examined the predisposing factors and
clinical characteristics of acute MH episodes and contrasted
these findings among 3 broad age groups across the spec-
trum of childhood. Our main hypothesis, that there are age-
based differences in clinical characteristics of acute MH,
was based on knowledge of differences in body composi-
tion, specifically percentage of skeletal muscle, throughout
childhood. During development, the most significant peri-
ods of skeletal muscle growth are after the stage of infancy
and then again at around the age of puberty.5,6 Since MH
is primarily a disease of muscle that predisposes to MH
susceptibility and determines severity of the acute MH
response, we postulated that older children would have
more severe effects of acute MH than younger children. Our
results appear to be consistent with this hypothesis.
Preoperative risk assessment for MH susceptibility has
been traditionally based on knowledge of case reports of
MH-associated diseases, and more recently, genetic linkage
studies.7 For individual patients, risk assessment is based
on family history of possible MH events. Although sub-
jects in the youngest age cohort at baseline tended to have
more generalized muscle weakness than the older cohorts,
most (> 80%) of all MH events occurred in phenotypically
normal children without a family history of MH-related
comorbidities.
For the entire cohort, the most common initial present-
ing signs of acute MH were tachycardia and hypercarbia.
However, we observed significant differences in additional
findings among age groups. In particular, the oldest aged
subjects were more likely to develop a higher maximum
temperature, a rapidly increasing temperature, higher peak

372
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Table 3.Treatments and Outcomes
Youngest age group Middle age group Oldest age group
(n = 35) (n = 163) (n = 66)
Characteristic n % n % n % P
General treatments
Volatile anesthetic discontinued 28 82.4 126 77.0 52 78.8 0.95
Anesthetic circuit changed 8 23.5 57 35.0 29 43.9 0.11
Hyperventilation 25 73.5 126 77.0 52 78.8 0.67
Active cooling 19 55.9 72 44.0 51 77.3 <0.001
Fluid loading 18 52.9 98 60.0 49 74.2 0.044
Cardiopulmonary resuscitation 1 2.9 11 6.0 5 7.6 0.72
Defibrillation 0 0.0 7 4.3 4 6.1 0.41
Pharmacologic treatments
Furosemide 4 11.8 28 17.2 17 25.8 0.17
Mannitol 6 17.6 34 20.9 20 30.3 0.24
Bicarbonate 10 29.4 57 35.0 29 43.9 0.27
Glucose/insulin 1 2.9 10 6.1 14 21.2 0.002
Amrinone 0 0.0 0 0.0 0 0.0
Bretylium 0 0.0 2 1.2 0 0.0 1
Vasopressin 1 2.9 1 0.6 2 3.0 0.2
Lidocaine 2 5.9 17 10.4 4 6.1 0.59
Dantrolene 27 79.4 111 68.1 55 83.3 0.051
Dantrolene initial dose (mg/kg)a 2.2 (0.97) 2.4 (1.9) 2.3 (1.1) 0.68
Total dantrolene dose (mg/kg)a 3.9 (1.5) 6.3 (4.6) 5.7 (4.2) 0.74
Dantrolene side effects 3 8.8 31 19.0 23 34.8 0.02
Hyperkalemia 0 0.0 2 1.2 5 7.6 0.03
Muscle weakness 3 8.8 17 10.4 16 24.2 0.02
Outcomes
Cardiac dysfunction 2 5.9 4 2.5 6 9.1 0.06
Death from sentinel MH event 0 0.0 6 3.7 4 6.1 0.35
Survived sentinel MH event 35 100.0 157 96.3 62 93.9 0.5
Developed recrudescence 8 22.9 18 11.5 12 19.7 0.19
Survived recrudescence 8 100.0 17 94.4 11 91.7 1
MH = malignant hyperthermia.
a
Mean (SD).

creatine kinase levels, and higher potassium levels. These
findings, taken together, indicate greater degrees of rhabdo-
myolysis, which can be explained by the greater overall per-
centage of baseline muscle composition in older children.
Inherent thermoregulatory differences during development
(i.e., age-related differences in rate of heat gain and dissi-
pation) may have also accounted for the significant differ-
ence in temperature levels observed across age groups.8,9
The youngest aged subjects developed lower blood gas pH
values and higher peak lactic acid levels than older subjects,
which may indicate less muscle reserve to buffer the occur-
rence of anaerobic metabolism during an acute MH event
in a population that is known to have higher resting meta-
bolic rates. The middle aged cohort of patients more often
displayed masseter spasm but less commonly displayed
the standard common findings of the oldest cohort. This
heterogeneous response may hinder diagnosis of MH in
thesecases.
Treatments of acute MH were similar across age groups,
except for some differences related to age-based physical
findings, such as higher temperatures and higher potassium
levels in older subjects, who were also more likely to receive
active cooling and glucose/insulin, respectively.
The incidence of death from acute MH in pediatric
patients is not well known. Rosero et al.1 reported 3 deaths
of 454 pediatric MH cases (0.66%), which was less than
their findings of an overall nationwide incidence (including
adults) of 11.7%. We demonstrated a higher overall death
rate (4.5%) of pediatric patients contained in the NAMHR.
Differences in methodological data collection as well as
reporting bias among studies are the most likely causes of
these inconsistent rates of death. Although we found that
the NAMHR contained no pediatric MH deaths before 1990,
this was likely biased by differences in recognition of MH
before that time. Therefore, our death rate among highly
suspected subjects is probably an underestimate.
Recrudescence after treatment was observed in 14.4% of
subjects and did not differ by age group. This is slightly less
than the overall rate of 20% (19.1% in subjects <12 years)
previously reported by Burkman et al.10 Although this latter
study also examined subjects included in the NAMHR, our
cohorts included additional years of collection and focused
on a larger group of pediatric subjects.
There are important limitations of data interpretation
when using databases such as the NAMHR. The NAMHR
is populated using cases from various different sources,
and most of MH cases that occur in North America are not
contained in the NAMHR. Furthermore, a number of cases
in the database occurred before the creation of the regis-
try (1987) and were entered into the current database in a
retrospective fashion. However, we are aware of no plau-
sible reason why these inherent biases would affect one age
group over the other.
In summary, our main hypothesis, that there are age-
related differences in clinical characteristics of acute
MH among different age cohorts during childhood, was

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Malignant Hyperthermia in Children
confirmed by analysis of subjects in the NAMHR. In general,
older subjects with presumed greater muscle mass demon-
strated a greater likelihood of higher body temperatures and
higher potassium levels, while the youngest subjects had
greater levels of metabolic acidosis. Our secondary hypoth-
esis, that we would be able to identify specific groups of chil-
dren at risk for development of acute MH, was unproven,
because nearly all children in all age groups were phenotypi-
cally normal before developing MH. E
DISCLOSURES
Name: Priscilla Nelson, MD.
Contribution: This author helped design and conduct the
study, analyze the data, and write the manuscript.
Attestation: Priscilla Nelson has seen the original study data,
reviewed the analysis of the data, and approved the final
manuscript.
Name: Ronald S. Litman, DO.
Contribution: This author helped design and conduct the
study, analyze the data, and write the manuscript.
Attestation: Ronald S. Litman has seen the original study data,
reviewed the analysis of the data, approved the final manu-
script, and is the author responsible for archiving the study files.
This manuscript was handled by: Peter J. Davis, MD.
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