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Prevalence of malignant hyperthermia diagnosis in obstetric patients in the United States, 2003 to 2014

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Background: The cost-benefit of stocking dantrolene in maternity units for treating malignant hyperthermia (MH) has been recently questioned because of the low incidence of MH crisis in the general population and the low utilization of general anesthesia in obstetrics. However, no study has examined the prevalence of MH susceptibility in obstetrics. This study aimed to assess the prevalence of MH diagnosis and associated factors in obstetric patients. Methods: Data for this study came from the National Inpatient Sample from 2003 to 2014, a 20% nationally representative sample of discharge records from community hospitals. A diagnosis of MH due to anesthesia was identified using the International Classification of Diseases, Ninth Revision, Clinical Modification code 995.86. MH prevalence was estimated according to the delivery mode and patient and hospital characteristics. Results: During the 12-year study period, 47,178,322 delivery-related discharges [including 15,175,127 (32.2%) cesarean deliveries] were identified. Of them, 215 recorded a diagnosis of MH, yielding a prevalence of 0.46 per 100,000 [95% confidence interval (CI), 0.40 to 0.52]. The prevalence of MH diagnosis in cesarean deliveries was 0.81 per 100,000 (95% CI, 0.67 to 0.97), compared with 0.29 per 100,000 (95% CI, 0.23 to 0.35) in vaginal deliveries (P < 0.001). Multivariable logistic regression revealed that cesarean delivery was associated with a significantly increased risk of MH diagnosis [adjusted rate ratio (aOR) 2.88; 95% CI, 2.19 to 3.80]. Prevalence of MH diagnosis was lower in Hispanics than in non-Hispanic whites (aOR 0.47; 95% CI, 0.29 to 0.76) and higher in the South than in the Northeast census regions (aOR 2.44; 95% CI, 1.50 to 3.96). Conclusion: The prevalence of MH-susceptibility is about 1 in 125,000 in cesarean deliveries, similar to the prevalence reported in non-obstetrical surgery inpatients. The findings of this study suggest that stocking dantrolene in maternity units is justified.
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R E S E A R C H A R T I C L E Open Access
Prevalence of malignant hyperthermia
diagnosis in obstetric patients in the United
States, 2003 to 2014
Jean Guglielminotti
1*
, Henry Rosenberg
2
and Guohua Li
1,3
Abstract
Background: The cost-benefit of stocking dantrolene in maternity units for treating malignant hyperthermia (MH)
has been recently questioned because of the low incidence of MH crisis in the general population and the low
utilization of general anesthesia in obstetrics. However, no study has examined the prevalence of MH susceptibility
in obstetrics. This study aimed to assess the prevalence of MH diagnosis and associated factors in obstetric patients.
Methods: Data for this study came from the National Inpatient Sample from 2003 to 2014, a 20% nationally
representative sample of discharge records from community hospitals. A diagnosis of MH due to anesthesia was
identified using the International Classification of Diseases, Ninth Revision, Clinical Modification code 995.86. MH
prevalence was estimated according to the delivery mode and patient and hospital characteristics.
Results: During the 12-year study period, 47,178,322 delivery-related discharges [including 15,175,127 (32.2%)
cesarean deliveries] were identified. Of them, 215 recorded a diagnosis of MH, yielding a prevalence of 0.46 per 100,
000 [95% confidence interval (CI), 0.40 to 0.52]. The prevalence of MH diagnosis in cesarean deliveries was 0.81 per
100,000 (95% CI, 0.67 to 0.97), compared with 0.29 per 100,000 (95% CI, 0.23 to 0.35) in vaginal deliveries
(P< 0.001). Multivariable logistic regression revealed that cesarean delivery was associated with a significantly
increased risk of MH diagnosis [adjusted rate ratio (aOR) 2.88; 95% CI, 2.19 to 3.80]. Prevalence of MH diagnosis was
lower in Hispanics than in non-Hispanic whites (aOR 0.47; 95% CI, 0.29 to 0.76) and higher in the South than in the
Northeast census regions (aOR 2.44; 95% CI, 1.50 to 3.96).
Conclusion: The prevalence of MH-susceptibility is about 1 in 125,000 in cesarean deliveries, similar to the
prevalence reported in non-obstetrical surgery inpatients. The findings of this study suggest that stocking
dantrolene in maternity units is justified.
Keywords: Childbirth, Malignant hyperthermia, Obstetrics
Background
Malignant hyperthermia (MH) is a pharmacogenetic dis-
order of the skeletal muscle triggered by halogenated in-
halational agents or the depolarizing muscle relaxant
succinylcholine [1,2]. Exposure to triggering agents can
lead to a rapid and uncontrolled calcium release in skel-
etal muscle cells cytoplasm and to a potentially lethal
hyper-metabolic crisis among susceptible patients [3].
Exposure to succinylcholine only, without volatile
anesthetics, can also triggers a MH crisis [3,4]. MH sus-
ceptibility is related to defects in the ryanodine receptor
1 (RyR1) or in the Ca
v
1.1 channel, two calcium channels
located in the sarcoplasmic reticulum membrane, or in
the Stac3 protein required for effective colocation of
RyR1 and Ca
v
1.1 [5]. Defects are caused by mutations in
the genes encoding for RyR1, Ca
v
1.1 (CACNA1S), or
Stac3. Despite the increased awareness of this condition,
improved intraoperative monitoring of end-tidal carbon
dioxide allowing early detection of MH crisis, and avail-
ability of an effective treatment (dantrolene), prognosis
of MH crisis is still poor. The 20072012 report from
the North American Malignant Hyperthermia Registry
© The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
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reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
* Correspondence: jg3481@cumc.columbia.edu
1
Department of Anesthesiology, Columbia University College of Physicians
and Surgeons, 622 West 168th Street, PH5-505, New York, NY 10032, USA
Full list of author information is available at the end of the article
Guglielminotti et al. BMC Anesthesiology (2020) 20:19
https://doi.org/10.1186/s12871-020-0934-0
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
of the Malignant Hyperthermia Association of the
United States indicates a case fatality rate of nearly 10%,
with increases in MH-associated morbidity and mortality
when dantrolene administration is delayed [3,6,7].
MH susceptibility is a rare disorder. Reported preva-
lence of MH diagnosis in studies using hospital discharge
records from administrative data ranges from 0.18 per
100,000 (95% confidence interval (CI), 0.120.25) in
ambulatory surgery center patients to 0.96 (95% CI,
0.751.41) in surgical inpatients [8,9]. The low fre-
quency of MH crises and the cost of stocking dantro-
lene have given rise to concern about the cost-benefit
of the recommendation of the Malignant Hyperther-
mia Association of the United States (MHAUS) that
dantrolene be made immediately available (for admin-
istration within 10 min) in operating room areas, es-
pecially in facilities with a low utilization of general
anesthesia and triggering agents such as maternity
units [10,11]. MHAUS is a patient safety and
advocacy organization and its recommendations are
used by accrediting agencies, such as the Joint
Commission, to assess preparedness for an MH event
during survey visits. However, no study has specific-
ally examined the prevalence of MH susceptibility in
obstetric patients [12].
Using a nationally representative sample of community
hospital discharges records in the United States between
2003 and 2014, we estimated the prevalence of MH
diagnosis in delivery-related discharges and assessed pa-
tient- and hospital-level factors associated with the
prevalence of MH diagnosis.
Methods
Data system and study sample
Data for this study came from the National Inpatient
Sample (NIS). NIS is part of the Healthcare Cost and
Utilization Project (HCUP) sponsored by the Agency for
Healthcare Research and Quality. It is a stratified sample
of approximately 20% of discharge records from com-
munity hospitals in the United States, excluding rehabili-
tation and long-term acute care hospitals. Community
hospitals are defined as all non-Federal, short-term,
general, and other specialty hospitals, excluding hospital
units of institutions.Included among community hospi-
tals are specialty hospitals such as obstetrics-gynecology,
ear-nose-throat, orthopedic, and pediatric institutions.
Also included are public hospitals and academic medical
centers. The sampling procedure is stratified according
to 6 hospital characteristics: census geographical area,
urban or rural location, ownership, teaching status, and
number of beds.
For each discharge, the NIS includes patient character-
istics, and up to 15 procedural codes and 30 diagnostic
codes defined in the International Classification of
Diseases, Ninth Revision, Clinical Modification (ICD-9-
CM). Discharges are weighted to permit inferences for a
nationally representative population. Sampling weights
before 2011 were updated in 2012 to take into consider-
ation the 2012 sampling re-design. Detailed information
on NIS data, methodology, and variables is publicly
available (http://www.hcup-us.ahrq.gov/nisoverview.jsp).
The study sample consisted of all discharges indicating
labor and delivery in the NIS between January 1, 2003,
and December 31, 2014. They were identified with a
combination of ICD-9-CM diagnosis and procedure
codes developed by Kuklina et al. [13]
Outcome
The outcome was a diagnosis of malignant hyperthermia
(MH) recorded in the discharge record, identified ac-
cording to the ICD-9-CM diagnosis code 995.86 (Ma-
lignant hyperthermia due to anesthesia).
Patient and hospital characteristics
Patient age, race or ethnicity, hospital length-of-stay, and
vital status at discharge were recorded directly from the
NIS. In the NIS, Hispanic ethnicity is considered as a
distinct racial/ethnic group. Excess hospital stay was de-
fined as a stay greater than the 90th percentile (3 days
for a vaginal delivery and 5 days for a cesarean delivery).
The Charlson comorbidity index and the comorbidity
index for obstetric patients were calculated using previ-
ously described ICD-9-CM algorithms [1416]. The co-
morbidity index for obstetric patients was designed
specifically for use in obstetric patient populations. It in-
cludes maternal age and 20 maternal conditions (e.g., se-
vere preeclampsia/eclampsia), that are predictive of
maternal end-organ injury or death during the delivery
hospitalization through 30 days postpartum. Delivery
was categorized as vaginal or cesarean delivery. The fol-
lowing hospital characteristics were recorded directly
from the NIS: location and teaching status (categorized
as rural, urban non-teaching and urban teaching) and
geographic region defined by the US Census Bureau
(Northeast, Midwest, South, and West).
Statistical analysis
Statistical analysis was performed with R version 3.5.0 (R
Foundation for Statistical Computing, Vienna, Austria)
and specific packages (survey for analysis of complex
survey samples). It followed the HCUP recommenda-
tions for the analysis of complex survey data [17].
Results are expressed as count (% or per 100,000).
Both unweighted and weighted counts were calculated
using individual discharge weight provided by the NIS.
Univariate comparison of categorical variables between
discharges with and without the diagnosis of MH used
Guglielminotti et al. BMC Anesthesiology (2020) 20:19 Page 2 of 9
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Chi-squared test and of continuous variables Wilcoxon
tests.
The prevalence of MH diagnosis was calculated overall
and according to the delivery mode (cesarean or vaginal
delivery). Furthermore, stratified analysis was performed
according to: 1) patient age, race, and comorbidity in-
dexes; 2) hospital location/teaching status and geo-
graphic region; and 3) 3 time periods (20032006,
20072010, and 20112014).
The adjusted odds ratios (aOR) of MH diagnosis were es-
timated using a weighted multivariable logistic regression
model with MH as the independent variable, the individual
dischargeweightprovidedbytheNISasweight,andthe
following variables as dependent variables: age, race,
Charlson comorbidity index, comorbidity index for obstet-
ric patients, mode of delivery (vaginal or cesarean), hospital
location and teaching status, geographic region, and the 3
time periods. For categorical variables with missing values,
a dummy indicator for missing values was created.
Results
During the 12-year study period, 9,892,712 delivery-
related discharges were identified in the NIS (weighted
number 47,178,322) (Fig. 1). Of them, 3,181,978 (32.2%)
were cesarean delivery discharges (weighted number 15,
175,127).
A diagnosis of MH was recorded in 46 delivery-related
discharges (weighted number 215), yielding a prevalence
of MH in obstetrics of 0.46 per 100,000 delivery-related
discharges (95% confidence interval (CI), 0.400.52)
(Fig. 2). In cesarean delivery discharges, a diagnosis of
MH was recorded in 26 cases (weighted number 123),
yielding a prevalence of 0.81 per 100,000 (95% CI, 0.67
0.97). In vaginal delivery discharges, a diagnosis of MH
was recorded in 20 cases (weighted number 92), yielding
a prevalence of 0.29 per 100,000 (95% CI, 0.230.35).
The prevalence of MH in cesarean delivery discharges
was significantly higher than in vaginal delivery dis-
charges [P-value < 0.001; crude OR 2.83; 95% CI, 2.16 to
3.71; aOR 2.88; 95% CI, 2.19 to 3.80].
Prevalence of MH in delivery-related discharges ac-
cording to patient characteristics, hospital characteris-
tics, and time period is presented in Table 1. On the
bivariate level, the prevalence of MH diagnosis was sig-
nificantly lower in Hispanics than in non-Hispanic
Whites and significantly higher in the Midwest and
South census regions than in the Northeast census re-
gion, and in rural hospitals than in urban hospitals. No
significant difference was observed across age groups,
comorbidity indexes groups, or time periods. Multivari-
able adjustment revealed two factors associated with
MH diagnosis: race/ethnicity (Hispanic versus non-
Hispanic White, aOR 0.47; 95% CI, 0.29 to 0.76) and
geographic census region (South versus Northeast, aOR
2.44; 95% CI, 1.50 to 3.96).
All the patients with a diagnosis of MH were alive
at the time of discharge. The proportion of discharges
with an excess length of hospital stay (i.e., 3 days for
a vaginal delivery and 5 days for a cesarean delivery)
was higher in discharges with a diagnosis of MH than
in discharges without a diagnosis of MH (15.3% ver-
sus 4.1%, P-value < 0.001).
National Inpatient Sample 2003-2014
93,377,054 discharges
(Nw459,398,938)
9,892,712 delivery-related discharges
(Nw47,178,322)
3,181,978 cesarean delivery discharges
(Nw15,175,127)
83,484,342 discharges excluded
(Nw412,220,616)
46 delivery-related discharges recording MH
(Nw215)
26 cesarean delivery discharges recording MH
(Nw 123)
Fig. 1 Flowchart of the study (MH: malignant hyperthermia; N
w
: weighted number)
Guglielminotti et al. BMC Anesthesiology (2020) 20:19 Page 3 of 9
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Discussion
This study was designed to help close a knowledge
gap in the epidemiology of MH. Specifically, we pro-
vide an estimate of the prevalence of MH diagnosis
in the obstetric patient population using a nationally
representative sample over a 12-year period. The
prevalence of 0.81 per 100,000 (95% CI, 0.67 to 0.97)
in cesarean delivery discharges is similar to the one
reported in non-obstetrical surgery inpatients. Using
New York State administrative data from 2001 to
2005, Brady et al. reported a prevalence of MH diag-
nosis in inpatient surgical discharges of 0.96 (95% CI,
0.67 to 1.24) [8]. The prevalence reported in the
present study is lower than the rate previously re-
ported using NIS data from 2000 to 2005 for the gen-
eral inpatient population (1.12 per 100,000, 95% CI,
1.08 to 1.17) [18]. The discrepancy is likely due to
thedifferencebythestudypopulationsasouranalysis
is restricted to obstetric patients and the prevalence
of MH diagnosis in women is only about a third of
the one in men [8,19].
We identified several patient- and hospital-level
characteristics associated with a higher prevalence of
MH diagnosis. We observed a lower prevalence of
MH diagnosis in Hispanics compared with non-
Hispanic White patients. To our knowledge, this find-
ing has not been reported before and if confirmed,
warrants further investigation to elicit the underlying
mechanisms. The lower prevalence of MH diagnosis
in Hispanic obstetric patients is unlikely due to a
lower utilization of general anesthesia and exposure
to triggering agents because two previous studies have
reported a higher utilization of general anesthesia in
minority patients, including Hispanics [20,21]. We
also observed a geographic variation in the prevalence
of MH diagnosis, with an elevated prevalence in the
South region. Geographical variation is explained by
the concentration of MH families in a given geo-
graphicarea[22]. Rosero et al. also observed a higher
prevalence of MH diagnosis in the South census re-
gion. Last, Rosero et al. reported an increase in the
prevalence in MH diagnosis between 2001 and 2005
[18]. We do not confirm this trend over the longer
20032014 time period. The study by Rosero started
just 2 years after the introduction of the ICD-9-CM
code for MH in 1998 and the increase in this study
may merely be related to the novelty of the code.
The prognosis of MH crisis remains poor with a fatal-
ity rate of nearly 10% and MH-associated morbidity and
mortality increased when dantrolene administration is
delayed [6,7]. Similar poor prognosis is observed in
studies using administrative data. In these studies, dis-
charges recording a diagnosis of MH have a fatality rate
ranging from 12 to 22% [8,18]. In our study, we
Fig. 2 Prevalence of malignant hyperthermia diagnosis in obstetrics in the 47,178,322 delivery-related discharges of the 20032014 National
Inpatient Sample, overall and according to the delivery mode. The vertical bars indicate the 95% confidence intervals
Guglielminotti et al. BMC Anesthesiology (2020) 20:19 Page 4 of 9
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Table 1 Prevalence of malignant hyperthermia (MH) according to selected characteristics in the 47,178,322 delivery-related discharges of the 20032014 National Inpatient
Sample
Discharges (N
w
) Discharges
with MH (N
w
)
Prevalence (per 100,000;
95% CI)
P-value Crude OR (95% CI) Adjusted OR
a
(95% CI)
Patient characteristic
Age (year) 0.67
19 4,399,524 18 0.41 (0.240.65) 0.96 (0.581.58) 1.02 (0.621.67)
2029 24,436,487 106 0.43 (0.360.52) Reference Reference
3039 17,029,672 86 0.51 (0.400.62) 1.17 (0.881.56) 1.15 (0.861.54)
40 1,310,043 --
b
--
b
(0.120.89) --
b
(0.332.11) 0.85 (0.332.16)
Race 0.006
White, Non-Hispanic 20,333,243 102 0.50 (0.410.61) Reference Reference
Black 5,268,451 24 0.46 (0.290.68) 0.90 (0.581.40) 0.82 (0.521.29)
Hispanic 9,035,771 20 0.22 (0.140.34) 0.44 (0.270.71) 0.47 (0.290.76)
Other 4,166,949 15 0.36 (0.200.59) 0.70 (0.401.20) 0.78 (0.451.35)
Charlson comorbidity index 0.85
0 47,035,792 215 0.46 (0.400.52) ––
1 142,530 0 0.00 (0.002.59) ––
Patient
Comorbidity index for
obstetric patients
0.92
0 or 1 41,467,932 188 0.45 (0.390.52) Reference Reference
2 5,707,789 27 0.47 (0.310.69) 1.06 (0.711.58) 0.79 (0.521.19)
Hospital
Location and teaching status 0.023
Rural 5,270,124 37 0.70 (0.490.97) 1.63 (1.122.39) 1.34 (0.911.98)
Urban non-teaching 19,230,712 83 0.43 (0.340.54) 1.01 (0.751.36) 0.96 (0.711.30)
Urban teaching 22,458,351 96 0.43 (0.350.52) Reference Reference
Hospital
Census region < 0.001
Northeast 7,678,323 20 0.26 (0.160.40) Reference Reference
Midwest 10,088,837 51 0.51 (0.380.66) 1.96 (1.173.29) 1.71 (0.992.93)
South 17,827,228 114 0.64 (0.530.77) 2.47 (1.543.98) 2.44 (1.503.96)
West 11,583,934 29 0.25 (0.170.36) 0.98 (0.55
1.73) 1.11 (0.621.98)
Time period 0.17
Year
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Table 1 Prevalence of malignant hyperthermia (MH) according to selected characteristics in the 47,178,322 delivery-related discharges of the 20032014 National Inpatient
Sample (Continued)
Discharges (N
w
) Discharges
with MH (N
w
)
Prevalence (per 100,000;
95% CI)
P-value Crude OR (95% CI) Adjusted OR
a
(95% CI)
20032006 16,163,993 86 0.53 (0.430.66) Reference Reference
20072010 16,049,577 69 0.43 (0.330.54) 0.81 (0.591.11) 0.81 (0.591.12)
20112014 14,964,752 59 0.39 (0.300.51) 0.75 (0.541.04) 0.77 (0.551.09)
Abbreviation: CI confidence interval, N
w
weighted number, OR odds ratio
a
Adjustment used all the variables listed in this table, along with the mode of delivery (vaginal or cesarean)
b
Because of HCUP data use agreement restrictions on small cell size, the number of observed cases and exact proportions are not presented
Guglielminotti et al. BMC Anesthesiology (2020) 20:19 Page 6 of 9
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identified no death in discharges with a diagnosis of
MH. A possible explanation for this finding is the young
age of the patients analyzed and the lack of associated
comorbidity; 98% of MH discharges were under 40 and
only 0.3% had a Charlson comorbidity index greater
than 1. By contrast, Brady et al. reported a 22% fatality
rate in discharges with a diagnosis of MH but 49% of the
MH discharges were older than 45 and 46% had a Charl-
son comorbidity index greater than 1 [8].
The Malignant Hyperthermia Association of the
United States recommends that dantrolene must be
available for all anesthetizing locations where MH
trigger agents are used.This recommendation also
applies to facilities where volatile agents are not avail-
able or administered, and succinylcholine is only
stocked on site for emergency purposes [3]. The cost
of an MH cart in maternity unit for responding to
MH crisis has been estimated at about $2000 per
year, including cost for the dantrolene itself, cost for
the cart and non-dantrolene items, and cost for MH
cart maintenance [10]. Ho et al. have recently ques-
tioned this recommendation based on cost-benefit
analysis of stocking dantrolene in maternity units
[10].ThelowincidenceofMHcrisisandthelow
utilization of general anesthesia and triggering agents
in obstetrics would not make stocking dantrolene pol-
icy cost-beneficial. Similar concerns have also been
raised in ambulatory surgery centers but two recent
studies support the dantrolene stocking policy in
these centers [3,23]. Of note, the prevalence of MH
susceptibility of 0.81 per 100,000 cesarean deliveries
(or 1 in 123,456 cases) reported in our study, similar
to the prevalence reported in non-obstetrical surgery
inpatients, suggests that stocking dantrolene in mater-
nity units is justified. In our opinion, the low annual
cost of a MH cart to treat a MH crisis in a maternity
unit ($2000 per year) and the prevention of maternal
death from a potentially treatable complication pro-
vide adequate justifications for stocking dantrolene in
maternity units. This is particularly relevant in the
current US context of implementing nationwide ini-
tiatives to reduce preventable severe maternal morbid-
ity and mortality [24].
It is worth noting the limitations with our study. First,
the NIS is a stratified sample of hospital discharges re-
cords and our study sample includes only 20% of child-
births during the study period. Second, identification of
MH diagnosis relies on the accuracy of coding in dis-
charges data and is susceptible to misclassification be-
cause of error or absence of coding. In a previous study
evaluating the accuracy of MH diagnosis in hospital dis-
charge records, we found that the ICD-9-CM code
995.86 (Malignant hyperthermia due to anesthesia)
corresponded to a MH crisis in 24% of the cases, to a
MH history in 47%, and to fever unrelated to MH in
24% [25]. Therefore, most of the cases with an MH diag-
nosis identified in the present study should be regarded
as MH susceptibility rather than incident MH episodes.
Lack of information on anesthetics exposed or dantro-
lene administration in the NIS dataset precludes us from
identifying incident MH episodes. In other words, an
ICD-9-CM-based approach favors sensitivity over speci-
ficity. Clinical registries such as the North American
Malignant Hyperthermia Registry represent more spe-
cific approaches but also suffer from limitations such as
the voluntary declarations of MH crisis with a risk of
under declaration and underestimation of the prevalence
of MH crisis. However, these two approaches should not
be viewed as antagonistic but as complementary. Third,
our unit of analysis was the discharge record and not the
patient. So, a patient with multiple hospitalizations dur-
ing this 12-year study could be included more than once
in our analysis. However, the National Inpatient Sample
is a 20% sample of discharges records, which decreases
the likelihood of a patient being sampled and included
multiple times. To further assess the potential impact of
repeated admissions of MH-susceptible patients, we
checked individually linked hospital discharge records
for 2,851,697 obstetric patients in New York State from
2003 to 2014; of the discharges with a diagnosis of MH,
none involved repeated admissions. Fourth, this study
was limited to obstetric patients because of the recent
controversy surrounding dantrolene stocking policy in
maternity units. There are other settings where trigger-
ing agents may be used, especially succinylcholine, such
as emergency departments or intensive care units and
where stocking dantrolene could be suggested. To date,
no study has specifically examined the prevalence of MH
diagnosis in these locations. Fifth, a diagnosis of MH in
women who underwent vaginal delivery may appear sur-
prising because a general anesthetic with exposure to
MH triggering agents is not required for an uncompli-
cated vaginal delivery. However, a general anesthetic
may be required after a vaginal delivery in some circum-
stances such as the removal of a retained placenta or an
exploration of the uterine cavity because of a postpartum
hemorrhage. Moreover, as indicated in our previous
study, most of the MH diagnoses in hospital discharge
records refer to positive MH history and susceptibility
rather than acute MH episodes [25]. These two factors
may explain why the prevalence of MH diagnosis in va-
ginal delivery was much lower than in cesarean delivery
(0.29 per 100,000 versus 0.81 per 100,000. Finally, the
NIS does not capture all childbirths occurring in the
country. For example, in 2014, the NIS included 3,828,
643 childbirths which corresponds to 96% of the 3,988,
076 births reported by the US National Center for
Health Statistics. The missing4% can be partially
Guglielminotti et al. BMC Anesthesiology (2020) 20:19 Page 7 of 9
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explained by out-of-hospital births (births at home or in
a birth center), which accounted for 1.5% of live births
in 2014.
Conclusions
The prevalence of MH-susceptibility is about 1 in 125,
000 in cesarean deliveries, similar to the prevalence re-
ported in non-obstetrical surgery inpatients. Results of
this study suggest that stocking dantrolene in maternity
units is justified.
Abbreviations
aOR: Adjusted Odds Ratio; CI: Confidence Interval; HCUP: Healthcare Cost
and Utilization Project; ICD-9-CM: International Classification of Diseases,
Ninth Revision, Clinical Modification; MH: Malignant Hyperthermia;
MHAUS: Malignant Hyperthermia Association of the United States;
NIS: National Inpatient Sample; OR: Odds Ratio; US: United States
Authorscontributions
JG had full access to all of the data in the study and takes responsibility for
the integrity of the data and the accuracy of the data analysis. He helped
design the study, conduct of the study, data collection, data analysis, and
manuscript preparation. GL helped design the study, conduct of the study,
interpretation of the results, and manuscript preparation. HR helped design
the study, conduct of the study, interpretation of the results, and manuscript
preparation. All authors read and approved the final manuscript.
Funding
This research was supported in part by the Malignant Hyperthermia
Association of the United States, Sherburne, NY. The Malignant Hyperthermia
Association of the United States had no role in study design, data collection,
data analysis, data interpretation, or writing of the manuscript.
Jean Guglielminotti is supported by an R03 from the Agency for Healthcare
Research and Quality (1 R03 HS02578701). The Agency for Healthcare
Research and Quality had no role in study design, data collection, data
analysis, data interpretation, or writing of the manuscript.
Availability of data and materials
The data that support the findings of this study are available from the
Healthcare Cost and Utilization Project (HCUP) (https://www.hcup-us.ahrq.
gov/) but restrictions apply to the availability of these data, which were used
under the HCUP data user agreement for the current study, and so are not
publicly available.
Ethics approval and consent to participate
The study protocol was granted exemption under 45 Code of Federal
Regulation 46 (not human subjects research) by the Institutional Review
Board of Columbia University Medical Center. The Strengthening The
Reporting of OBservational studies in Epidemiology (STROBE) and the
Reporting of studies Conducted using Observational Routinely-collected
health Data (RECORD) statements were followed [26,27].. Administrative per-
mission to access the data was granted by the Healthcare Cost and
Utilization Project (HCUP).
Consent for publication
Not applicable.
Competing interests
Dr. Henry Rosenberg is the president of the Malignant Hyperthermia
Association of the United States. The content is solely the responsibility of
this author and does not necessarily represent the official views of the
Malignant Hyperthermia Association of the United States. The remaining
authors declare no competing interests.
Author details
1
Department of Anesthesiology, Columbia University College of Physicians
and Surgeons, 622 West 168th Street, PH5-505, New York, NY 10032, USA.
2
the Malignant Hyperthermia Association of the United States, Sherburne, NY
13460, USA.
3
Department of Epidemiology, Columbia University Mailman
School of Public Health, 722 West 168th Street, New York, NY 10032, USA.
Received: 12 February 2019 Accepted: 9 January 2020
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... MH is a rare, autosomal dominant disorder that presents as a hypermetabolic response to volatile anesthetic and depolarizing neuromuscular blocking drugs. The incidence of MH in an obstetric patient undergoing CD is approximately 1:125,000, 27 and this life-threatening anesthetic-induced emergency requires immediate treatment to decrease significant morbidity and mortality associated with it. The Malignant Hyperthermia Association of the United States (MHAUS) recommends dantrolene (the drug used to treat MH) be available for administration within 10 minutes of the decision to treat 28 and MHAUS has developed a list of equipment and drugs to be stored in an MH cart. ...
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Utilization of emergency resources in obstetrics can help to optimize health care providers' care to pregnant and postpartum patients. There is a vast array of resources with various accessibility modalities that can be used before, during, and/or after an obstetric emergency. These resources can also be included as teaching material to increase knowledge and awareness with the aim to reduce maternal morbidity and mortality and improve patient outcomes.
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Malignant hyperthermia (MH) is a rare but deleterious anaesthetic emergency that has an autosomal dominant inheritance. Successful management of the MH-susceptible fetus hinges on early suspicion and preparation. This case highlights the importance of knowing paternal anaesthetic risk as well as maternal in the parturient population. Paternal anaesthetic history is paramount in this situation, especially with a normal maternal risk, and preparation of the patient, staff and equipment is at the centre of the peripartum management of these patients.
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Objective: Cesarean delivery is common, involves two patients, has numerous multi-disciplinary health care providers involved in the delivery management, but has variable levels of anesthesia and health services implementation for decreasing maternal hypothermia and the maternal and neonatal morbidity (and mortality). Limited implementation for either of the ERAS-CD or the ERAC guidelines, for inadvertent or preventive maternal hypothermia, is likely to be occurring on labor delivery floors. This Quality Improvement (QI) review focuses on cesarean delivery and maternal hypothermia. Methods: This quality and safety initiative used SQUIRE 2.0 methodology and concurrent PubMed searches to identify systematic review, meta-analysis, topic directed studies, additional published cohorts in the topic area not included in SR/MA, limited case reports that had specific clinical outcomes related to maternal hypothermia and fetal effects. Results: Two quality and safety improvement guidelines have defined the hypothermia activity element differently, with ERAS-CD recommending to prevent hypothermia, while ERAC recommending to maintain normothermia. The peer-reviewed literature indicates that the knowledge associated with surgical hypothermia outcome is known but it is not implemented for maternal cesarean delivery care. Increased maternal-effect recognition, surveillance, triage, and evidenced-based protocol management is required for the maternal - neonatal dyad undergoing cesarean delivery for the clinical reduction/prevention of neonatal hypothermia that has proven evidence-based maternal morbidity and neonatal morbidity/mortality. Conclusion: TEAM-based anesthesia, obstetrical, neonatology-pediatrics and nursing research collaboration is required through quality-safety-ERAS-ERAC directed processes. Healthcare system recognition and financial support is required for maternal-fetal-neonatal hypothermia prevention protocols implementation.
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Full-text available
What we already know about this topic: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Although dantrolene effectively treats malignant hyperthermia (MH), discrepant recommendations exist concerning dantrolene availability. Whereas Malignant Hyperthermia Association of the United States guidelines state dantrolene must be available within 10 min of the decision to treat MH wherever volatile anesthetics or succinylcholine are administered, a Society for Ambulatory Anesthesia protocol permits Class B ambulatory facilities to stock succinylcholine for airway rescue without dantrolene. The authors investigated (1) succinylcholine use rates, including for airway rescue, in anesthetizing/sedating locations; (2) whether succinylcholine without volatile anesthetics triggers MH warranting dantrolene; and (3) the relationship between dantrolene administration and MH morbidity/mortality. Methods: The authors performed focused analyses of the Multicenter Perioperative Outcomes Group (2005 through 2016), North American MH Registry (2013 through 2016), and Anesthesia Closed Claims Project (1970 through 2014) databases, as well as a systematic literature review (1987 through 2017). The authors used difficult mask ventilation (grades III and IV) as a surrogate for airway rescue. MH experts judged dantrolene treatment. For MH morbidity/mortality analyses, the authors included U.S. and Canadian cases that were fulminant or scored 20 or higher on the clinical grading scale and in which volatile anesthetics or succinylcholine were given. Results: Among 6,368,356 queried outcomes cases, 246,904 (3.9%) received succinylcholine without volatile agents. Succinylcholine was used in 46% (n = 710) of grade IV mask ventilation cases (median dose, 100 mg, 1.2 mg/kg). Succinylcholine without volatile anesthetics triggered 24 MH cases, 13 requiring dantrolene. Among 310 anesthetic-triggered MH cases, morbidity was 20 to 37%. Treatment delay increased complications every 10 min, reaching 100% with a 50-min delay. Overall mortality was 1 to 10%; 15 U.S. patients died, including 4 after anesthetics in freestanding facilities. Conclusions: Providers use succinylcholine commonly, including during difficult mask ventilation. Succinylcholine administered without volatile anesthetics may trigger MH events requiring dantrolene. Delayed dantrolene treatment increases the likelihood of MH complications. The data reported herein support stocking dantrolene wherever succinylcholine or volatile anesthetics may be used.
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Full-text available
Background: The Malignant Hyperthermia Association of the United States recommends that dantrolene be available for administration within 10 min. One approach to dantrolene availability is a malignant hyperthermia cart, stocked with dantrolene, other drugs, and supplies. However, this may not be of cost benefit for maternity units, where triggering agents are rarely used. Methods: The authors performed a cost-benefit analysis of maintaining a malignant hyperthermia cart versus a malignant hyperthermia cart readily available within the hospital versus an initial dantrolene dose of 250 mg, on every maternity unit in the United States. A decision-tree model was used to estimate the expected number of lives saved, and this benefit was compared against the expected costs of the policy. Results: We found that maintaining a malignant hyperthermia cart in every maternity unit in the United States would reduce morbidity and mortality costs by $3,304,641 per year nationally but would cost $5,927,040 annually. Sensitivity analyses showed that our results were largely driven by the extremely low incidence of general anesthesia. If cesarean delivery rates in the United States remained at 32% of all births, the general anesthetic rate would have to be greater than 11% to achieve cost benefit. The only cost-effective strategy is to keep a 250-mg dose of dantrolene on the unit for starting therapy. Conclusions: It is not of cost benefit to maintain a fully stocked malignant hyperthermia cart with a full supply of dantrolene within 10 min of maternity units. We recommend that hospitals institute alternative strategies (e.g., maintain a small supply of dantrolene on the maternity unit for starting treatment).
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(Anesthesiology. 2018;129:249–259) Understanding the cost-benefit trade-off of maintaining a malignant hyperthermia (MH) cart has important policy implications. The Malignant Hyperthermia Association of the United States recommends that operating room areas have dantrolene immediately available for administration (within 10 min). One approach to dantrolene availability is an MH cart, stocked with dantrolene, other drugs, and supplies, which is cost-effective in areas with a substantial number of general anesthetics. However, labor and delivery units rarely use MH—triggering drugs. If you consider a hospital with 6000 deliveries in a year with a 30% cesarean delivery rate and a 5% general anesthesia rate, general anesthesia will be used <100 times in 1 year. Such a low incidence prompts the question of whether the standard proposed is necessary for maternity units, because, to meet this standard, many maternity units should have their own MH cart. One may question if the resources used to maintain an MH cart may be better utilized on other initiatives that may have a more significant impact on maternal morbidity or mortality (such as a difficult airway cart).
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This review identifies disease states associated with malignant hyperthermia susceptibility based on genotypic and phenotypic findings, and a framework is established for clinicians to identify a potentially malignant hyperthermia-susceptible patient. Copyright © 2017, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved.