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Copyright © 2015 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
February 2016 • Volume 122 • Number 2 www.anesthesia-analgesia.org 449
Copyright © 2015 International Anesthesia Research Society
DOI: 10.1213/ANE.0000000000001054
Malignant hyperthermia (MH) is an autosomal-
dominant genetic disorder of the skeletal muscle,
linked to ryanodine receptor (RYR1) gene muta-
tions.1 This pharmacogenetic clinical syndrome is triggered
by sensitivity to volatile inhaled anesthetic gases (e.g., sevo-
urane, desurane, isourane) and the depolarizing neuro-
muscular blocking drug succinylcholine, leading to skeletal
muscle hypermetabolism.2 Epidemiologic data on MH are
scant. The prevalence of MH due to anesthesia in surgical
patients treated in New York State hospitals is estimated to
be approximately 1 per 100,000.3 There is little information
about the prevalence of MH in patients treated in the ambu-
latory care setting.
Since the early 1980s advances in medical technol-
ogy, the changes in payment arrangements and increasing
health care costs have contributed to the increase of ambu-
latory surgery centers (ASCs) in the United States.4 ASCs
are health care facilities that provide same-day surgical care
outside the hospital setting, including diagnostic and pre-
ventive procedures. They are considered to be more practi-
cal and generally less expensive than hospitals.4 According
to the National Center for Health Statistics of the Centers
for Disease Control and Prevention, in 2010, ambulatory
surgery cases totaled 18.7 million, accounting for 63.6%
of all surgical procedures.5 From 1996 to 2006, the rate of
visits to freestanding ASCs tripled, whereas the rate in hos-
pital-based ASCs remained unchanged.4 According to the
Healthcare Cost and Utilization Project (HCUP), the num-
ber of ASCs increased from 336 in 1985 to 6167 in 2008.6 To
ensure patient safety in ambulatory care settings, it is neces-
sary to better understand the epidemiology of MH in ASCs.7
The purpose of this study was to estimate the prevalence of
MH diagnosis and characterize factors associated with MH
diagnosis recorded in a large sample of ASC discharges.
METHODS
This study meets the criteria for the Protection of Human
Subjects exemption 4 (research involving preexisting data)
of the United States Code of Federal Regulations (45 CFR
46.101). The study was deemed exempt from review by the
IRB’s Administrative Review Committee at the Columbia
University Medical Center (New York, NY).
Data Source
Data for this study came from HCUP State Ambulatory
Surgery Databases (SASD) for New York State from 2002 to
2011. SASD contains the New York State’s ambulatory sur-
gery discharge records, including abstracts from hospital-
owned ASCs and nonhospital-owned freestanding ASC
facilities.6 A facility is considered hospital based if any 1 of
the 3 criteria is met6: (1) an American Hospital Association
(AHA) hospital identier can be determined; (2) the facility
provides inpatient data to the HCUP project, but no AHA
hospital identier can be determined; and (3) documentation
BACKGROUND: Malignant hyperthermia (MH) is a rare yet potentially fatal pharmacogenetic dis-
order triggered by exposure to inhaled anesthetics and the depolarizing neuromuscular blocking
drug succinylcholine. Epidemiologic research on MH is largely limited to inpatients. In this study,
we examined the prevalence of recorded MH diagnosis in patients discharged from ambulatory
surgery centers (ASCs).
METHODS: We analyzed the New York State Ambulatory Surger y Dataset for the years 2002 to
2011 and identied patients with a discharge diagnosis of MH due to anesthesia by using the
International Classification of Disease, Ninth Revision, Clinical Modication code 995.86. MH
prevalence was assessed by demographic, clinical, and ASC characteristics.
RESULTS: During the study period, 31 of 17,092,765 discharges from ASCs had a recorded
diagnosis of MH, yielding a prevalence of 0.18 per 100,000 discharges (95% condence inter-
val, 0.12–0.25). The prevalence of recorded MH diagnosis per discharge differed signicantly
across age groups and surgical procedure categories. All patients with a recorded diagnosis of
MH were from hospital-based ASCs and were discharged alive from ASCs.
CONCLUSIONS: The prevalence of recorded MH diagnosis in ASC patients is approximately 1 per
500,000 and varies considerably with surgical procedures. (Anesth Analg 2016;122:449–53)
Prevalence of Malignant Hyperthermia Diagnosis in
New York State Ambulatory Surgery Center Discharge
Records 2002 to 2011
Zhen Lu, MPH,* Henry Rosenberg, MD,† Joanne E. Brady, PhD,* and Guohua Li, MD, DrPH*‡
From the *Department of Epidemiology, Columbia University Mailman
School of Public Health, New York, New York; †Department of Medical
Education and Clinical Research, Saint Barnabas Medical Center, Livingston,
New Jersey; and ‡Department of Anesthesiology, Columbia University
College of Physicians and Surgeons, New York, New York.
Accepted for publication September 8, 2015.
Funding: This study was supported in part by the Malignant Hyperthermia
Association of the United States, Sherburne, NY, and by Grant 1 R49 CE002096
from the National Center for Injury Prevention and Control, Centers for
Disease Control and Prevention to the Center for Injury Epidemiology and
Prevention at Columbia University. Its contents are solely the responsibil-
ity of the authors and do not necessarily represent the ofcial views of the
Centers for Disease Control and Prevention.
Conict of Interest: See Disclosures at the end of the article.
Reprints will not be available from the authors.
Address correspondence to Guohua Li, MD, DrPH, Department of Anesthe-
siology, Columbia University College of Physicians and Surgeons, 622 West
168th St., PH5-505, New York, NY 10032. Address e-mail to GL2240@cumc.
columbia.edu.
Copyright © 2015 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
Malignant Hyperthermia in Ambulatory Surgery
450 www.anesthesia-analgesia.org ANESTHESIA & ANALGESIA
provided by the data source clearly indicates the facility is
hospital based. An AHA hospital identier cannot always
be determined for hospital-based facilities because hospi-
tals may not be matched to the AHA. The SASD database
contains clinical and nonclinical information on all patients
including patient diagnoses and procedures, admission
and discharge status, patient demographics (e.g., gender,
age, and race), payment source (Medicare, Medicaid, pri-
vate insurance, and uninsured), and some hospital char-
acteristics. HCUP state databases are discharge-level (not
patient) les in which each record represents 1 ambula-
tory surgical visit. The Agency for Healthcare Research
and Quality aggregates International Classication of Disease,
Ninth Revision, Clinical Modication (ICD-9-CM) diag-
nostic coding into meaningful clinical groups: the Clinical
Classication Software (CCS) codes.8 According to HCUP,
the record selection criteria for ambulatory surgery dis-
charges varied from 2009 to 2011, resulting in uctuation in
record counts in these years.a
Study Sample
The study sample consisted of all ASC discharges in New
York State from 2002 through 2011. MH cases were identi-
ed by screening all the discharge diagnoses using the ICD-
9-CM code 995.86 to indicate MH due to anesthesia.
Statistical Analysis
The prevalence of MH due to anesthesia was calculated
based on all ASC discharges in SASD from 2002 to 2011.
MH prevalence was examined according to patient char-
acteristics including age, sex, payment type, exposure to
anesthesia, and comorbid conditions. Comorbidities were
identied by applying the Charlson Comorbidity Score to
ICD-9-CM codes in the data sets.9,10 We calculated the prev-
alence of MH for 5-year intervals and examined trends in
MH prevalence from 2002 to 2011 and also calculated the
95% condence intervals (CIs) using the normal approxima-
tion method.11 Comparisons of prevalence among different
patient groups were performed with SAS version 9.4 (SAS
Institute, Cary, NC); and χ2 or Fisher exact test was used
to compare categorical variables. Statistical signicance was
dened as P < 0.05.
RESULTS
Prevalence
The SASD database for 2002 to 2011 contained 17,092,765
ASC discharge records; of them, 31 had an MH diagnosis.
The overall prevalence of MH was 0.18 (95% CI, 0.12–0.25)
per 100,000 discharges (Table 1). The difference in MH prev-
alence across all groups of exposure to anesthesia, including
exposure to no anesthesia, was not statistically signicant
(P = 0.065; Table 1). However, the prevalence of MH for
patients who received general anesthesia was 2.5 times (95%
CI, 1.12–5.56, P = 0.025) the prevalence for those receiving
other anesthesia including local and regional anesthesia
(Table 1). The estimated prevalence of MH diagnosis per
100,000 discharges increased from 0.11 (95% CI, 0.03–0.18)
in 2002 to 2006 to 0.24 (95% CI, 0.14–0.34) in 2007 to 2011 (P
= 0.001; Table 1). The difference in MH prevalence between
sexes was not statistically signicant (P = 0.76; Table 1).
Through cross-referencing revisit les (except for 2002
SASD that was unavailable) and other discharge variables
such as race, birth year, and birth month, all 31 patients with
a diagnosis of MH were deemed unique individual patients.
Based on revisit les of 2009 to 2011, 28.5% of ASC patients
had repeat visits within 3 years.
Characteristics of MH Cases
Of the 31 patients with a diagnosis of MH, 53.6% were
younger than 45 years, 88.0% were Caucasian, and 55.0%
were male (Table1). All of the patients with a diagnosis of
MH were discharged to home or self-care with the excep-
tion of 1 patient being transferred to a short-term hospital.
Based on the Charlson-Deyo Comorbidity Score ≥1, 26.0% of
the MH patients had at least 1 signicant preexisting medi-
cal condition. Of 31 MH patients, 50.0% received general
anesthesia, whereas 33.0% received administration of other
anesthesia, such as local and regional anesthesia (Table 1).
More than half of those with an MH diagnosis had private
insurance as the primary payer for receiving medical ser-
vices from ASCs, whereas approximately 39.0% of those
diagnosed as MH susceptible were covered by Medicare
and Medicaid (Table 1). All 31 patients with a diagnosis of
MH were alive at the time of discharge from the ASCs. All
patients diagnosed with MH were recorded in discharges
from hospital-based ASCs. Based on the CCS codes, the dif-
ference in MH prevalence across all diagnosis categories
was not statistically signicant (P=0.68; Table2). The MH
prevalence per discharge differed signicantly across all
CCS surgery categories (P= 0.01), with the highest preva-
lence (1.66 per 100,000 discharges; 95% CI, 0.00–3.39) being
found in surgeries of the ear, such as tympanoplasty, myrin-
gotomy, and mastoidectomy (Fig.1).
Ambulatory Services
The number of freestanding ASCs in New York State
increased almost threefold within 10 years, whereas the
number of hospital-based ASCs remained unchanged
(Fig.2). Furthermore, the number of surgical visits to free-
standing ASCs increased over the decade. Based on the
SASD of 2002 to 2007, 92% of the ASC visits were surgical
visits, and the remaining were likely preoperative assess-
ment visits and postoperative follow-up visits because there
were no procedure codes recorded for these visits. The top
3 surgery categories performed in ASCs from 2002 to 2007
were digestive system (29.7%), musculoskeletal system
(12.5%), and eye (12.2%).
DISCUSSION
This study provides valuable information for understand-
ing the epidemiologic patterns of MH in ASC settings. The
results indicate that the prevalence of MH among ASCs in
New York State between 2002 and 2011 is 0.18 per 100,000
discharges (95% CI, 0.12–0.25). In previous studies, the
prevalence of MH in hospital surgical patients was found
to be approximately 1 per 100,000 in New York State3 and
aDetails of the record selection criteria are provided in the New York State
Ambulatory Surgery Databases le composition notes. Available at http://
www.hcup-us.ahrq.gov/db/state/sasddist/sasddist_filecompny.jsp.
Accessed July 20, 2014.
Copyright © 2015 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
February 2016 • Volume 122 • Number 2 www.anesthesia-analgesia.org 451
1.3 patients per 100,000 in the United States.12 To our knowl-
edge, this study is among the rst to estimate the prevalence
of MH in ambulatory settings. The results indicate that the
overall prevalence of MH in ASCs in New York State is
much less than reported in hospital surgical patients, prob-
ably due to enhanced MH awareness and preferential treat-
ment of MH-susceptible patients in the inpatient setting. It
is important to note that the prevalence of MH discussed
in this study encompasses both MH susceptibility and MH
incidents.
Our results also indicate that 16.7% of patients with
an MH diagnosis did not receive anesthesia. Because
patients in ASCs usually undergo low-risk surgical pro-
cedures such as extraction of lens, which are less com-
plex and less invasive than those performed in hospital
settings, the anesthesia care often involves only regional
and local anesthetics, decreasing the risk of triggering
MH among MH-susceptible patients. Compared with
hospitals, freestanding ASCs have fewer resources and
capabilities to provide advanced treatment for urgent and
Table 1. Prevalence and 95% CIs of Malignant Hyperthermia due to Anesthesia by Patient Characteristics in
Ambulatory Surgery Centers, New York State, 2002 to 2011
Patient characteristics
Number of
discharges
Number of discharges
with MH diagnosis
Prevalence per
100,000 discharges 95% CI
Age (y)a
<18 1,216,824 —b0.41 0.05–0.77
18–44 4,282,667 13 0.30 0.14–0.47
45–64 6,493,986 —b0.09 0.02–0.17
65+ 5,016,563 —b0.14 0.04–0.24
Sexa
Female 7,259,368 14 0.19 0.09–0.29
Male 9,829,732 17 0.17 0.09–0.26
Charlson-Deyo Comorbidity Index
0 15,211,242 23 0.15 0.09–0.21
1+ 1,881,523 —b0.43 0.13–0.72
Exposure to anesthesiac
General anesthesia 4,629,061 15 0.32 0.02–0.26
Other anesthesia 7,708,034 —b0.13 0.05–0.21
No anesthesia 3,621,951 —b0.14 0.02–0.26
Payment typea
Medicare/Medicaid 6,400,123 12 0.19 0.08–0.29
Private insurance 8,833,991 16 0.18 0.09–0.27
Other 1,533,246 —b0.20 0.00–0.42
Year of discharge
2002–2006 7,439,713 —b0.11 0.03–0.18
2007–2011 9,653,052 23 0.24 0.14–0.34
ASC type
Hospital based 14,434,194 31 0.22 0.14–0.29
Freestanding 2,658,571 0 0 —
Total 17,092,765 31 0.18 0.12–0.25
ASC=ambulatory surgery center ; CI=condence interval; MH=malignant hyperthermia.
aThere were 82,484 discharges with age less than 1 year, 241 (<0.00%) discharges with missing information on age; 0.02% discharges with missing information
on sex; and 325,405 (1.90%) discharges with missing information on payment type.
bThese data are not presented as the report of data for any subgroup with 10 or fewer subjects is prohibited by the Healthcare Cost and Utilization Project State
Ambulatory Surgery Databases data use agreement.
cThere were 1,133,719 (6.63%) discharges and 1 case with missing information on exposure to anesthesia.
Table 2. Prevalence and 95% CIs of Malignant Hyperthermia due to Anesthesia by Clinical Diagnosis
Categorya in Ambulatory Surgery Centers, New York State, 2002 to 2011
Diagnosis category
Number of
discharges
Prevalence per
100,000 discharges 95% CI
Respiratory system 640,412 0.63 0.01–1.24
Complication pregnancy, birth, puerperium 597,551 0.34 0.00–0.80
Digestive system 2,995,634 0.23 0.06–0.41
Musculoskeletal, Connective tissue 1,877,673 0.21 0.00–0.42
Nervous system, sense organs 2,531,522 0.20 0.02–0.37
Neoplasm 2,133,060 0.19 0.00–0.37
Genitourinary system 1,595,996 0.19 0.00–0.40
Circulatory system 1,069,211 0.09 0.00–0.28
Other 1,446,160 0.07 0.00–0.21
Total 17,092,698b0.18 0.00–0.25
CCS = Clinical Classication Software; CI = condence interval.
aCCS is used to aggregate clinical diagnosis categories. Individual malignant hyperthermia cases are not presented because the report of data for any subgroup
with 10 or fewer subjects is prohibited by the State Ambulatory Surgery Databases data use agreement.
bThere were 67 discharges missing a CCS diagnosis category.
Copyright © 2015 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
Malignant Hyperthermia in Ambulatory Surgery
452 www.anesthesia-analgesia.org ANESTHESIA & ANALGESIA
life-threatening events. Many ASCs do not have imme-
diate laboratory access to make a diagnosis and moni-
tor its treatment.13 Therefore, MH-susceptible patients or
patients who have been diagnosed with MH might choose
to undergo surgery without general anesthesia or in hos-
pital settings that are better equipped to manage a MH cri-
sis, providing another plausible explanation for the lower
prevalence of MH in ASCs.
Consistent with previous studies of inpatient popula-
tions, the age group for patients with the highest prevalence
of MH in ASCs is <45 years.12 Although previous studies
in hospital surgery patients reported a higher prevalence
of MH in males than in females,3,12 this study did not nd
a signicant difference between sexes in the prevalence of
MH in ASCs, due in part to the modest number of MH
cases included in the study. One possible explanation for
the divergent nding from hospital surgery patients might
be differences in utilization patterns of ASCs between
sexes. Another nding of the study is that the category of
ear surgery has the highest prevalence of MH. Insertion
of tympanostomy tubes is the most common ambulatory
surgery performed on children in the United States.14
One possible reason for the increased prevalence of MH
in patients undergoing ear surgery might be that these
patients are more likely to develop postoperative fever,
and thus, the fever may be misdiagnosed as MH. It is
also possible that the heightened prevalence of MH in ear
surgery resulted from confounding factors, such as type
of anesthesia. Further research using larger datasets and
more sophisticated statistical techniques may help under-
stand whether there is a causal relationship between ear
surgery and excess risk of MH.
Our study has several limitations. First, our data sets
did not contain variables that would allow us to distin-
guish incident MH events from visits where patients have
a family history of MH or documented MH susceptibility.
ICD-9 codes are likely to be more accurate for calculating
disease prevalence than for calculating disease incidence
because incidence requires identication of new cases or
cases without previous documentation.15 The prevalence of
MH as found in this study is the combined cases of inci-
dence and MH-susceptible individuals during their stay
in the ASCs. As suggested by an earlier study, to improve
specicity of searches for incident MH events using admin-
istrative databases such as SASD, it might be meaningful to
include information on surgical procedure and dantrolene
administration.16 Another approach is to review medical
records for patients with a recorded diagnosis of MH in
combination with ICD codes because clinical evidence will
be useful in differentiating incident MH cases from MH
susceptibility in ASCs.15 The absence of ICD-9-CM surgical
procedures since 2008 in the data set made it impossible
for us to examine the associations between MH prevalence
and types of surgical procedures among ambulatory sur-
gery patients in recent years.
Second, SASDs are proprietary databases that focus on
discharge diagnoses. The accuracy and completeness of
MH diagnosis and coding may vary across facilities. Based
on a recent study, the most common reason for inaccurate
MH coding for hospital discharge records is because of high
fever unrelated to anesthesia.16 The study also nds that
prevalence of MH susceptibility is more likely to be cap-
tured accurately by ICD-9-CM code than MH incidence,16
implying that by using administrative databases such as
SASD, the MH prevalence found in our study could be
reecting a larger proportion of MH-susceptible patients
rather than MH incidence. Since the diagnosis code was rst
introduced in 1997,16 familiarity of MH coding among phy-
sicians and medical coders might vary signicantly across
ASCs, leading to potential underreporting, misdiagnosis, or
miscoding of MH cases in our data sets. As demonstrated by
our study, the number of freestanding ASCs has increased
threefold over the decade, but no MH case was reported
from any freestanding ASCs. This observation suggests that
compared with hospital-based ASCs in which physician
experts or well-trained medical coders could identify and
report MH cases, freestanding ASCs might lack experienced
medical staff to recognize the disease and record MH cases
accurately. Further evaluation of the sensitivity and speci-
city of MH coding in outpatient administrative databases
might help improve the accuracy of epidemiologic studies
in ambulatory care settings.
Figure 1. Prevalence per 100,000 discharges and SE of malignant
hyperthermia due to anesthesia by surgical procedure category in
ambulatory surgery centers, New York State, 2002 to 2007. Clinical
Classication Software is used to aggregate surgical procedure cat-
egories. Eight percent of discharges were missing information on
surgical procedure category.
Figure 2. Number of ambulatory surger y center (ASC) discharges in
New York State, 2002 to 2011.
Copyright © 2015 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
February 2016 • Volume 122 • Number 2 www.anesthesia-analgesia.org 453
Third, the prevalence reported in our study was based
on the number of ambulatory surgery discharges, rather
than unique individual patients. MH patients who were
transferred from other health care facilities and died in
the emergency room before admission to the hospital are
not included in the SASD. Unplanned admissions to hos-
pitals after ambulatory surgery were estimated to occur
in 0.5% to 1.5% of cases.17,18 Finally, because of the mod-
est number of MH cases in the study sample, our analy-
sis was limited to descriptive statistics. In the absence of
multivariate analysis, it was not possible for us to iden-
tify the risk factors for MH in ASCs with adjustment for
confounding factors.
Despite these limitations, the large sample size of the
SASD database enable epidemiologic analyses of a rare
medical condition such as MH. Among ASC discharges in
New York State, the overall prevalence of MH was less than
among hospital discharges. Even though our study shows
that all 31 patients with a recorded diagnosis of MH were
discharged alive from ASCs, we cannot conclude that it is
safe for patients with MH susceptibility to have surgery in
an ambulatory setting. Conversely, MH susceptibility is not
a contraindication for anesthesia and surgery in an ambu-
latory setting. All facilities where anesthesia is provided
should be prepared to recognize, treat, and manage an MH
crisis according to the guidelines established by accredit-
ing agencies and the Malignant Hyperthermia Association
of the United States. The ndings of our study should be
valuable for informing health care policy and developing
clinical guidelines to ensure patient safety in ASCs. E
DISCLOSURES
Name: Zhen Lu, MPH.
Contribution: This author reviewed the literature, analyzed the
data, and wrote the draft manuscript.
Attestation: Zhen Lu has seen the original study data, reviewed
the analysis of the data, and approved the nal manuscript.
Conicts of Interest: Zhen Lu declares no conicts of interest.
Name: Henry Rosenberg, MD.
Contribution: This author helped design the study, interpret
the ndings, and revise the manuscript.
Attestation: Henry Rosenberg has seen the original study
data, reviewed the analysis of the data, and approved the nal
manuscript.
Conicts of Interest: Henry Rosenberg reported a conict of
interest with Eagle Pharmaceuticals (Woodcliff Lakes, NJ) and
received a 1-time speaking fee from Eagle Pharmaceuticals, a
company that manufactures Ryanodex, a concentrated formu-
lation of dantrolene approved for the treatment of malignant
hyperthermia.
Name: Joanne E. Brady, PhD.
Contribution: This author helped supervise the statistical anal-
ysis, interpret the results, and write the manuscript.
Attestation: Joanne E. Brady has seen the original study data,
reviewed the analysis of the data, and approved the nal
manuscript.
Conicts of Interest: Joanne E. Brady declares no conicts of
interest.
Name: Guohua Li, MD, DrPH.
Contribution: This author designed the study, acquired the
data, supervised the data analysis, and oversaw the develop-
ment of the manuscript.
Attestation: Guohua Li has seen the original study data,
reviewed the analysis of the data, approved the nal manuscript,
and is the author responsible for archiving the study les.
Conicts of Interest: Guohua Li declares no conicts of interest.
This manuscript was handled by: Sorin J. Brull, MD.
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