EDUCATION
Bruno Riou, M.D., Ph.D., Editor
Case Scenario: Bronchospasm during Anesthetic Induction
Pascale Dewachter, M.D., Ph.D.,* Claudie Mouton-Faivre, M.D.,† Charles W. Emala, M.D.,‡
Sadek Beloucif, M.D., Ph.D.§
This article has been selected for the ANESTHESIOLOGY CME Program. Learning
objectives and disclosure and ordering information can be found in the CME
section at the front of this issue.
B RONCHOSPASM, the clinical feature of exacerbated
underlying airway hyperreactivity, has the potential to
become an anesthetic disaster. During the perioperative pe-
riod, bronchospasm usually arises during induction of anes-
thesia but may also be detected at any stage of the anesthetic
course. Accordingly, prompt recognition and appropriate
treatment are crucial for an uneventful patient outcome.
Perioperative bronchospasm (i.e., the clinical expression of
exacerbated underlying airway reactivity) may be associated
with type E immunoglobulin (IgE)-mediated anaphylaxis or
may occur as an independent clinical entity, triggered by
either mechanical and/or pharmacologic factors. Whatever
the clinical circumstances, different triggers are identified in
the occurrence of perioperative bronchospasm with asthma,
a chronic inflammatory disorder of the airways frequently
involved. The purpose of this clinical scenario is to discuss
the key points of perioperative bronchospasm.
* Staff Anesthesiologist, Service d’Anesthésie-Réanimation and
SAMU de Paris, Université Paris-Descartes, INSERM UMRS-970 and
Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de
Paris, Paris, France; † Staff Internist and Allergologist, Pôle
d’Anesthésie-Réanimation Chirurgicale, CHU Hôpital Central,
Nancy, France; ‡ Professor, Department of Anesthesiology, College
of Physicians and Surgeons, Columbia University, New York, New
York; § Professor, Service d’Anesthésie-Réanimation, Université
Paris 13 & Hôpital Avicenne, Assistance Publique Hôpitaux de Paris.
Received from the Université Paris-Descartes, Paris, France. Sub-
mitted for publication August 28, 2010. Accepted for publication Feb-
ruary 11, 2011. Support was provided solely from institutional and/or
departmental sources. Figures 1–3 in this article were prepared by
Annemarie B. Johnson, C.M.I., Medical Illustrator, Wake Forest Univer-
sity School of Medicine Creative Communications, Wake Forest Uni-
versity Medical Center, Winston-Salem, North Carolina.
Address correspondence to Dr. Dewachter: Service
d’Anesthésie-Réanimation & SAMU de Paris, Hôpital Necker-
Enfants Malades, 149 Rue de Sèvres 75743 Paris Cedex 15,
France. pascale.dewachter@yahoo.fr. This article may be ac-
cessed for personal use at no charge through the Journal Web
site, www.anesthesiology.org.
Copyright © 2011, the American Society of Anesthesiologists, Inc. Lippincott
Williams & Wilkins. Anesthesiology 2011; 114:1200 –10
Anesthesiology, V 114 • No 5
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Case Report
A 25-yr-old woman with morbid obesity (body mass index:
54 kg/m2) and noninsulin-dependent diabetes was sched-
uled for cochlear implant surgery. She had two previous sur-
geries without incident during childhood. She denied any
history of atopy or drug allergy. Chest auscultation was nor-
mal before anesthesia. She was premedicated with hy-
droxyzine (100 mg orally) the day before and 1 h before
anesthesia, which was induced with sufentanil (20 ␮g intra-
venously) and propofol (350 mg intravenously). Tracheal
intubation (Cormack and Lehane grade I) was facilitated
with succinylcholine (130 mg intravenously). After tracheal
intubation was performed, chest auscultation revealed a
complete absence of bilateral breath sounds. Initial concen-
trations of end-tidal carbon dioxide (ETCO2) were low. Be-
cause an esophageal intubation was suspected, the patient
was immediately extubated and mask ventilation attempted.
Mask ventilation was difficult to perform because of dramat-
ically decreased lung compliance, whereas ETCO2 demon-
strated a marked prolonged expiratory upstroke of the cap-
nogram. Therefore, bronchospasm was considered. Rapid
arterial oxygen desaturation (oxygen saturation measured by
pulse oximetry [SpO2], 55%) followed by arterial hypoten-
sion (from 130/75 to 50/20 mmHg) associated with a mod-
erate tachycardia (100 beats/min) occurred in less than 5 min
after the onset of bronchospasm. Concomitantly, titrated
epinephrine (two intravenous boluses of 100 ␮g each) along
with fluid therapy with crystalloids (lactated Ringer’s solu-
tion, 1,000 ml) corrected the cardiovascular disturbances (ar-
terial blood pressure, 110/50 mmHg; heart rate, 110 beats/
min) while at the same time ventilation became easier to
perform along with the return of audible wheezing over both
lung fields. As arterial blood pressure was restored, a localized
(face and upper thorax) erythema occurred. Hydrocortisone
(200 mg) was intravenously administered. A blood sample
was obtained to measure serum tryptase concentrations, 40
and 90 min after the clinical reaction. Surgery was post-
1200 May 2011
 EDUCATION
poned, and the patient was transferred to the intensive care
unit. No additional supportive vasopressor therapy was re-
quired. Respiratory symptoms resolved within 2 h after in-
haled ␤2-agonist (salbutamol; i.e., albuterol) and intravenous
corticoids (hydrocortisone, cumulative dose: 800 mg over
24 h). Subsequent clinical outcome was uneventful, and the
patient was discharged home the following day and returned
6 weeks later for allergologic assessment (see section III).
Discussion
I. Diagnosis and Differential Diagnosis of Intraoperative
Wheezing/Bronchospasm
Bronchospasm encountered during the perioperative period
and especially after induction/intubation may involve an im-
mediate hypersensitivity reaction including IgE-mediated
anaphylaxis or a nonallergic mechanism triggered by factors
such as mechanical (i.e., intubation-induced bronchospasm)
or pharmacologic-induced (via histamine-releasing drugs
such as atracurium or mivacurium) bronchoconstriction in
patients with uncontrolled underlying airway hyperreactiv-
ity.1,2 Chest auscultation should be done to confirm wheezing,
whereas decreased or absent breath sounds suggest critically low
airflow.3 The differential diagnosis includes inadequate anesthe-
sia, mucous plugging of the airway, esophageal intubation,
kinked or obstructed tube/circuit, and pulmonary aspiration.3
Unilateral wheezing suggests endobronchial intubation or an
obstructed tube by a foreign body (such as a tooth).3 If the
clinical symptoms fail to resolve despite appropriate therapy,
other etiologies such as pulmonary edema or pneumothorax
should also be considered.
II. Diagnosis of a Perioperative Immediate Reaction
Immediate hypersensitivity is a clinical entity evoking allergy
that varies in severity1 and is subdivided into nonallergic
hypersensitivity (called anaphylactoid reaction by the Amer-
ican Academy of Allergy Asthma and Immunology) where an
immune mechanism is excluded, and allergic hypersensitivity
(also called IgE-mediated anaphylaxis).4 By definition, im-
mediate hypersensitivity occurs within 60 min after the in-
jection/introduction of the culprit agent.1 The initial diag-
nosis remains presumptive, whereas the etiologic diagnosis is
linked to a triad including clinical features (the description of
the clinical features according to the adapted Ring and Mess-
mer储 clinical severity scale); blood tests (tryptase level mea-
surements, serum-specific IgEs); and postoperative skin tests
with the suspected drugs or agents.1
储 Grade I: Erythema, urticaria with or without angioedema;
grade II: cutaneous-mucous signs ⫾ hypotension ⫾ tachycardia ⫾
dyspnea ⫾ gastrointestinal disturbances; grade III: cardiovascular
collapse, tachycardia, or bradycardia ⫾ cardiac dysrythmia ⫾ broncho-
spasm ⫾ cutaneous-mucous signs ⫾ gastrointestinal disturbances;
grade IV: cardiac arrest.
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III. Etiology of This Perioperative Immediate
Hypersensitivity in the Current Case
The sudden occurrence of bronchospasm after anesthetic in-
duction, with cardiovascular disturbances and cutaneous
signs, clinically suggested a drug-induced anaphylactic reac-
tion. Succinylcholine-induced anaphylaxis was the most
likely etiology, because neuromuscular blocking agents are
the most frequent agents involved in perioperative anaphy-
laxis in adults.1,5 Skin testing remained negative in response
to propofol, sufentanil, succinylcholine, and latex solutions
(Allerbio, Varennes en Argonne, France and Stallergènes,
Antony, France). Tryptase levels (ImmunoCAP, Phadia
SAS, Uppsala, Sweden) were unchanged (5.4 ␮g 䡠 l⫺1 and
4.3 ␮g 䡠 l⫺1; N less than 13.5 ␮g 䡠 l⫺1) in blood samples
obtained 40 and 90 min, respectively, after the onset of the
reaction. Serum-specific IgEs (ImmunoCAP) against succi-
nylcholine and latex were not detectable. Specific serum IgE
against quaternary ammonium was slightly increased (2.08
kU/L, N less than 0.1). A basophil activation test was also
performed and analyzed using a FACSCanto II flow cytom-
eter (Becton-Dickinson, Rungis, France). Succinylcholine
induced neither CD63 nor CD203c up-regulation.
Clinical Considerations. The chronology of evolving clinical
features is crucial to understand the pathophysiologic mech-
anism of an immediate hypersensitivity reaction.
Cardiovascular disturbance is the hallmark of severe IgE-
mediated anaphylaxis. In patients with neuromuscular
blocking agent-induced perioperative anaphylaxis, cardio-
vascular signs are usually the inaugural clinical event and
occur within minutes after the drug challenge. These cardio-
vascular signs may be associated with or followed by bron-
chospasm in 19 – 40% of patients, more likely in those with
underlying asthma or chronic obstructive pulmonary dis-
ease.1 Drug-induced anaphylactic bronchospasm may occur
either before or after instrumentation of the airway2 (fig. 1).
Latex-induced anaphylaxis typically occurs in patients
with a history of atopy.6 Because atopy is the strongest iden-
tifiable predisposing factor for the development of asthma,7
severe clinical features occurring during latex-induced ana-
phylaxis usually involve cardiovascular signs followed by or
associated with bronchospasm and cutaneous signs.8 As latex
proteins are slowly absorbed, latex-induced anaphylaxis usu-
ally occurs up to 30 – 60 min after the beginning of surgery
(i.e., mucous membrane exposure).8
Acute increases in airway responsiveness may also occur in
the absence of an antigen challenge and result from irritation
of the well-innervated upper airway by a foreign body (e.g.,
endotracheal tube or suction catheter).2 Thus, nonallergic
bronchospasm immediately follows nonspecific stimuli and
usually is not associated with cardiovascular symptoms2 (fig. 1).
Nevertheless, positive end-expiratory pressure with severe bron-
chospasm may lead to a decrease in venous return and hence of
cardiac output. In addition, the association of hypoxia and re-
spiratory failure from inadequate ventilation may lead to
cardiovascular collapse.9
1201 Dewachter et al.

Fig. 1. Pathophysiologic mechanisms involved during perioperative immediate hypersensitivity reaction according to the onset
of bronchospasm when compared with endotracheal tube insertion.
IV. Distinguishing the Pathophysiologic Mechanism of
Perioperative Bronchospasm Clinically
Four clinical variables were identified as independent predic-
tors of allergic compared with nonallergic perioperative
bronchospasm: the presence of any cutaneous symptoms;
shock; episodes of desaturation; and the prolonged duration
of clinical features (longer than 60 min).2 Compared with
that of patients who did not present with these “predictive”
signs as part of the clinical syndrome, the occurrence of hy-
potension or episodes of oxygen desaturation were 27 and 21
times, respectively, more likely to be associated with IgE-
mediated anaphylaxis. In addition, symptom duration lon-
ger than 60 min or the presence of skin changes was two and
seven times, respectively, more likely to be associated with
IgE-mediated anaphylaxis.2 In the current case, inaugural
severe bronchospasm triggered by endotracheal tube inser-
tion and followed by cardiovascular collapse, likely related to
subsequent hypoxemia after the patient’s extubation, yields
clinical insight into the pathophysiologic mechanism of the
reaction and suggests nonallergic bronchospasm. Cutaneous
signs, such as erythema, are not specific for IgE-mediated
anaphylaxis per se and may also be observed during nonaller-
gic bronchospasm.2 The morbid obesity of the patient is
of clinical interest and could also have been a precipitating
factor of rapid arterial desaturation despite appropriate
preoxygenation.
Allergologic Assessment: Blood Tests and Skin Testing. A
tryptase increase is specific for mast cell activation such as
that occurring during IgE-mediated anaphylaxis.1 Increased
tryptase levels appear to distinguish clearly between allergic
and nonallergic perioperative bronchospasm.2 Thus, Fisher2
suggested that an allergologic assessment is unnecessary in
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Bronchospasm during Anesthetic Induction
patients with isolated bronchospasm occurring after airway
instrumentation without an increase in tryptase. In the cur-
rent case, allergic mast cell activation was ruled out because
tryptase levels measured within the recommended time
frame remained unchanged. Skin tests were negative in re-
sponse to the medications received (i.e., propofol, sufentanil,
and succinylcholine) as well as latex. These results were cor-
roborated by basophil activation tests showing an absence of
CD63 and CD203c up-regulation with succinylcholine, rul-
ing out basophil sensitization by specific IgE toward succi-
nylcholine and undetectable specific serum IgEs against suc-
cinylcholine. Serum IgEs against quaternary ammonium was
slightly increased (2.08 kU/L, N less than 0.1), but these
assays appear to be less sensitive than skin tests and do not
prove that the drug/agent is responsible for the reaction.10
Succinylcholine-induced anaphylaxis was therefore ruled
out according to clinical, biologic, and allergologic evidence.
This is of particular importance because succinylcholine is
thereby allowed to be used for future anesthetics in this pa-
tient. In turn, uncontrolled asthma was suggested to be the
main trigger of this nonallergic bronchospasm after endotra-
cheal tube insertion. Wheezing induced by bronchial infec-
tion during childhood or triggered by cold weather and ex-
ercise in adulthood was elicited from the patient’s history
during the postoperative evaluation.
V. Asthma Is a Frequently Underdiagnosed Condition
Asthma is one of the most common chronic airway diseases
worldwide, with a higher prevalence and incidence in the
Western world.11 The estimated annual death rate world-
wide is 250,000.12 However, this condition frequently re-
mains underdiagnosed. In 2008, the following definition for
1202 Dewachter et al.
 EDUCATION
asthma was suggested: “Asthma is a chronic disorder of the
airway in which many cells and cellular elements play a role. The
chronic inflammation is associated with airway responsiveness
that leads to recurrent episodes of wheezing, breathlessness, chest
tightness and coughing, particularly at night or in the early
morning. These episodes are usually associated with widespread,
but variable airflow obstruction within the lung, that is often
reversible either spontaneously or with treatment.”12 This pro-
posal was ratified in the United States.7 Accordingly, a Eu-
ropean and American Task Force issued by the correspond-
ing Respiratory Societies suggested that the definition of
asthma includes two domains (symptoms and variable airway
obstruction) being assessed in clinical practice, with two ad-
ditional domains (airway inflammation and hyperrespon-
siveness) characterizing the underlying disease. An individual
may have features of any or all of these domains.13 Airway
hyperresponsiveness is induced by a variety of changes in the
airway and sustained by underlying airway inflammation, the
hallmark of asthma.
Recently, a crucial modification in the approach to
asthma management was proposed with a classification by
the level of asthma control (controlled, partly controlled, or
uncontrolled) rather than asthma severity per se while linking
the classification of asthma control to asthma treatment.12
Two Main Phenotypes of Asthma Can be Distinguished.
Two main phenotypes of asthma, allergic and nonallergic,
are most commonly discussed; overlap may occur within
these groups.14
Allergic Asthma. The largest overall phenotype in children
and adults is allergic asthma. Although allergic asthma is a
chronic and often lifelong disease, its onset occurs primarily
in early childhood. However, more than 50% of asthma is
allergic in adults.4 It results from immunologic reactions,
mostly initiated by IgE antibodies, and is also called IgE-
mediated allergic asthma. Genetic factors may promote the
development of allergic asthma (inheritable component).
Environmental factors such as tobacco smoke, air pollutants,
and exposure to allergens including indoor (mites, animals,
plant origin, e.g., ficus), outdoor (pollens, molds) or occupa-
tional allergens may trigger asthma. Obesity, diet, and a hy-
giene hypothesis may also trigger asthma.11 Thus, any poten-
tial risk factor must eventually interact with an underlying
genetically determined pathway to result in the manifesta-
tion of disease (epigenetic component). However, atopy, the
genetic predisposition for the development of an IgE-medi-
ated response to common aeroallergens, is the strongest iden-
tifiable predisposing factor for developing asthma.7 Two ma-
jor factors such as airborne allergens and viral respiratory
infections seem to be the most important in the develop-
ment, persistence, and possibly the severity of allergic
asthma.7
Allergic Rhinitis and Allergic Asthma Belong to the Same
Airway Disease. The effect of allergic rhinitis on asthma
should also be highlighted15 because the link of this distur-
bance with asthma remains poorly understood. Rhinitis is
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characterized by nasal symptoms including sneezing, nasal
blockage, and/or itching of the nose; is either intermittent or
permanent; and is classified as mild, moderate, or severe.15
More than 80% of asthmatic individuals have rhinitis, and
10 – 40% of patients with rhinitis have asthma. A combined
strategy should ideally be used to treat the upper and lower
airway diseases (allergen avoidance is crucial but inhaled/
intranasal corticosteroid is the most consistently effective
long-term control therapy attenuating airway inflamma-
tion). 7,15 Because the presence of asthma must be considered
in all patients with rhinitis, those with severe and/or persis-
tent uncontrolled allergic rhinitis should be evaluated for
asthma before surgery.
Nonallergic Asthma: Aspirin-induced Asthma. The other
main variant of asthma in adults includes a widely underdi-
agnosed phenotype not seen in childhood, such as aspirin-
induced asthma. Aspirin-induced asthma is characterized by
eosinophilic rhinosinusitis, nasal polyposis, aspirin or non-
steroidal antiinflammatory drug sensitivity, and asthma.
Asthma and sensitivity to aspirin usually appear approxi-
mately 1–5 yr after the onset of rhinitis,16 whereas rhinor-
rhea, nasal congestion, and anosmia are usually the first clin-
ical features of aspirin-induced asthma. This phenotype
results from the inhibition of cyclooxygenase enzymes by
aspirin-like drugs in the airway of sensitive patients and is not
sustained by an allergic mechanism.16
VI. Perioperative Bronchospasm
Asthma is considered to be more prevalent in westernized
countries.11 Surprisingly, no academic society of anesthesi-
ology issued from the European or the North American con-
tinents has published recommendations concerning the peri-
operative management of the asthmatic patient. The
literature on this topic remains scarce.
Epidemiology of Perioperative Bronchospasm. The occur-
rence of perioperative bronchospasm has been reported in up
to 9% of asthmatic patients given general anesthesia, mainly
after endotracheal tube insertion.17 Smoking also represents
a major risk. Compared with that of nonsmokers, the relative
risk of perioperative bronchospasm in smokers appears
higher in females and in young smokers (16 –39 yrs old) and
is higher in patients with chronic bronchitis than in asymp-
tomatic patients.18
Why and When Does Perioperative Bronchospasm Occur?
Of the 4,000 incidents reported in Australia, 103 reports of
perioperative bronchospasm (3%) showed that an allergic
mechanism was less frequently involved (21%) than a non-
allergic mechanism (79%).19 Among these nonallergic cases,
44% occurred during the induction of anesthesia, 36% dur-
ing the maintenance phase, and 20% during the emergence/
recovery stage. During induction of anesthesia, broncho-
spasm was mainly related to airway irritation (64%), whereas
remaining causes were due to tube misplacement (17%),
aspiration (11%), and other pulmonary edema or unknown
causes (8%). During the maintenance stage of anesthesia,
1203 Dewachter et al.

allergy (34%), endotracheal tube malposition (23%), airway
irritation (11%), and aspiration with a laryngeal mask airway
(9%) together accounted for almost 80% of the occurrences
of bronchospasm. During induction or maintenance of an-
esthesia, bronchospasm caused by airway irritation occurred
more frequently in patients who had one or more predispos-
ing factors such as asthma, heavy smoking, or bronchitis.
Others showed that an allergic mechanism accounted for
60% of the cases in patients experiencing bronchospasm dur-
ing induction of anesthesia.2 A previous history of asthma
was present in 50% and 60% of patients with nonallergic and
allergic bronchospasm, respectively. Thus, uncontrolled
asthma/chronic obstructive pulmonary disease is frequently
involved with either pathophysiologic mechanisms (allergic
vs. nonallergic), regardless of the stage of anesthesia (induc-
tion or maintenance).
Morbidity and Mortality Rates. Respiratory events ac-
counted for 28% of claims concerning anesthesia-related
brain damage and death in the United States.20 In this series,
bronchospasm was included in the other categories and to-
gether corresponded to 11% of total respiratory events. In
the United Kingdom, respiratory and airway incidents ac-
counted for 3% and 8%, respectively, of all claims including
severe and fatal outcomes.21 Bronchospasm was not detailed.
Nevertheless, airway incidents belong to the claims with the
highest overall cost and respiratory complications with the
highest mean cost per closed claim. Seven percent of anes-
thesia-related deaths were attributed to bronchospasm in
France.22
In conclusion, bronchospasm remains a serious life-
threatening perioperative event. Its dramatic consequences
involving brain damage or death may be partly explained by
substandard care and/or inadequate practice and system fail-
ures.20,22 Optimal management of perioperative broncho-
spasm should therefore be encouraged through teaching ap-
plications such as an anesthesia simulator to compensate for
the low frequency with which the average practitioner would
encounter severe bronchospasm during routine clinical care.
Basic Science: Mechanisms of Reflex-induced Broncho-
constriction. The mechanisms of asthmatic exacerbations
resulting in bronchoconstriction are complex and involve
airway nerves, smooth muscle, epithelium, and inflamma-
tory cells. However, reflex-induced bronchoconstriction in-
duced by irritation of the upper airway by a foreign body
such as an endotracheal tube is modulated by synapse of
afferent sensory pathways in the nucleus of the solitary tract,
which projects to the airway-related vagal preganglionic neu-
rons. The excitatory neurotransmitter glutamate modulates
stimulation of the nucleus of the solitary tract and airway-
related vagal preganglionic neurons, whereas inhibitory
nerves releasing ␥-aminobutyric acid project from the nu-
cleus of the solitary tract to the airway-related vagal pregan-
glionic neurons.23 The excitatory outflow from the airway-
related vagal preganglionic neurons back to the airway is
carried in the vagus nerve and results in acetylcholine release
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Bronchospasm during Anesthetic Induction
onto airway structures, most prominently the M3 muscarinic
receptor on airway smooth muscle that induces airway con-
striction.24 Thus, the initial airway irritant stimulus sends an
afferent signal to the brainstem, resulting in an efferent signal
traveling in the vagus and releasing acetylcholine in the air-
way (fig. 2). Because acetylcholine acting on M3 muscarinic
receptors on airway smooth muscle is a key mechanistic com-
ponent of reflex-induced bronchoconstriction, the use of an-
timuscarinic-inhaled medications (e.g., ipratropium or
tiotropium) should be advantageous to prevent or treat this
phenomenon.25 In addition, nonadrenergic noncholinergic
nerves releasing tachykinins, vasoactive intestinal peptide,
and calcitonin gene-related peptide may participate in this
reflex arc and/or locally release the procontractile neurotrans-
mitters via activation of interneurons in the airway.26 A re-
cent study suggests that propofol preferentially relaxes tachy-
kinin-induced airway constriction in airway smooth
muscle.27 It has long been clinically recognized that the
depth of anesthesia modulates the likelihood of eliciting re-
flex-induced bronchoconstriction, but the pharmacologic
mechanisms by which this occurs are unknown. Propofol28
and the volatile inhalational anesthetics (with the exception
of desflurane) are known to be clinically effective at prevent-
ing reflex-induced bronchoconstriction or attenuating intra-
operative bronchoconstriction.29 These agents share activity
at inhibitory ␥-aminobutyric acid-A chloride channels30;
thus, it has been speculated that modulation of ␥-aminobu-
tyric acid input to the airway-related vagal preganglionic
neurons from the nucleus of the solitary tract and higher
central nervous system centers may be a mechanism by which
deepening anesthesia prevents or relieves reflex-induced
bronchoconstriction. Moreover, both propofol and inhala-
tional anesthetics have direct bronchodilatory effects at the
level of airway smooth muscle itself 31 acting via ␥-aminobu-
tyric acid-A channels32 or modulating calcium sensitivity of
the contractile proteins.33 However, despite these protective
effects of intravenous propofol and the adequate induction
dose used in the current case, reflex-induced bronchocon-
striction developed in this patient who had previously unrec-
ognized and untreated asthma.
VII. Obesity and Asthma: Is There Any Relationship?
There is increasing evidence linking obesity, defined as a
body mass index of at least 30 kg/m2, to asthma and airway
hyperreactivity in both children and adults.34 Both asthma
and obesity are systemic inflammatory states. Their develop-
ment seems to be determined early in life, with this associa-
tion not being mediated through atopy.34 In turn, potential
explanations for the parallel increase of asthma and obesity
might involve genetic, mechanical, hormonal, and environ-
mental factors. Accordingly, chromosomal regions with loci
common to obesity and asthma phenotypes have been iden-
tified. Reduced functional residual capacity and decreased
tidal volume as a result of obesity result in greater contractile
responses of airway smooth muscle, causing potentially in-
1204 Dewachter et al.
 EDUCATION

Fig. 2. Schematic diagram of airway irritant reflex-induced bronchoconstriction by tracheal intubation. The upper airway is well
innervated by afferent sensory pathways synapsing in the nucleus of the solitary tract (nTS), which projects excitatory
glutaminergic and inhibitory ␥-aminobutyric acid-A (GABA)-ergic neurons to the airway-related vagal preganglionic neurons
(AVPN). Parasympathetic preganglionic efferents travel in the vagus nerve to release acetylcholine onto M3 muscarinic
receptors on airway smooth muscle inducing bronchoconstriction.

creased airway reactivity.34 –35 Although gastroesophageal re-
flux resulting from obesity may potentially trigger a latent
asthmatic condition,11 this condition was ruled out with an
esophageal transit test.
Hormonal influences may also be involved as the effect of
obesity on asthma is stronger in females than males.35 In
addition, the hormone leptin produced by adipocytes and
that acts in the hypothalamus to signal satiety35 has effects on
immune cell function and inflammation. Serum leptin levels
in adulthood were shown to be higher in women than men
with a higher prevalence of asthma.34 The association be-
tween asthma and obesity may be of recent origin, suggesting
that recent changes in lifestyle and diet are now associated
with both asthma and obesity.11 However, weight gain an-
tedates asthma or asthma symptoms, ruling out the hypoth-
esis that this association might be the result of reduced phys-
ical activity by asthmatic patients leading to obesity.34
VIII. Sleep-disordered Breathing and Asthma
Sleep-disordered breathing is more prevalent in asthmatic
individuals than in those without asthma, whereas sleep-
disordered breathing and asthma share common risk factors
such as obesity.35 The reasons for the association between
both conditions remain unknown.35 Asthma remains under-
diagnosed in obese patients because respiratory symptoms
are frequently attributed to being overweight, as was the case
in our patient. In such patients, underlying airway hyperre-
activity should be cautiously assessed during the preoperative
evaluation (see section IX).
In the current case and after the clinical postanesthetic
evaluation, borderline sleep-disordered breathing was also
detected through polysomnography.
IX. Prevention of Perioperative Bronchospasm
The controls of airway inflammation and corresponding asthma
symptoms are essential to optimize perioperative and postoper-
ative care. The National Asthma Education and Prevention
Program Expert Panel Report 3 recommends that the level of
asthma control, medication use (especially oral systemic corti-
costeroid within the past 6 months), and pulmonary function
be reviewed before surgery.7 The Global Initiative for Asthma
guidelines suggest that perioperative and postoperative compli-
cations rely on the severity of asthma at the time of surgery, the
type of surgery (thoracic and upper abdominal surgeries being at
increased risk), and modalities of anesthesia (general anesthesia
with tracheal intubation is at higher risk).12 Others suggest that
uncontrolled or poorly controlled asthma may be assessed
through the degree of asthma control (increased use of inhaled
short-acting ␤2-agonists, previous/current use of inhaled corti-
costeroids, recent use of oral/injected corticosteroids, recent ex-
acerbations of asthma symptoms, emergency department or
hospital visit within the last months) and potential risks or com-
plication factors (recent infection of the respiratory tract, previ-
ous bronchospasm after intubation, pulmonary complications
during/after previous surgical procedure, long-term use of a sys-
temic corticosteroid for severe asthma, associated gastroesopha-
geal reflux or smoking).36 The common key point of these rec-
ommendations focuses on the level of asthma control before

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surgery7,12,36 as uncontrolled asthma is considered to be the
main risk factor for bronchoconstriction during surgery.36
Preoperative Clinical and Physical Examination. Careful
clinical and physical examinations are therefore crucial for
preoperative pulmonary risk assessment to identify findings
suggestive of unrecognized underlying airway hyperreactiv-
ity. Decreased breath sounds as seen in markedly decreased
expiratory airflow, sibilants, rhonchi, and prolonged expira-
tory phase, as well as recent and/or frequent exacerbations of
respiratory symptoms including wheezing, cough, exercise
intolerance, unexplained dyspnea, and gastroesophageal re-
flux disease should raise concern during the preoperative
evaluation.3 Among these different findings, decreased
breath sounds, dullness to percussion, wheezing, rhonchi,
and a prolonged expiratory phase predict an increase in the
risk of perioperative pulmonary complications.37 Thus, poorly
controlled asthma usually favors perioperative pulmonary com-
plications3,36,38 whereas airway instrumentation may induce
life-threatening bronchospasm, perioperative complications,
and prolonged intensive care treatment.20 Conversely, con-
trolled asthma does not promote additional risk.36,38
Corticosteroids Are the Key Point of Antiasthma Long-
term Control Therapy. Long-term therapy is used daily to
achieve and maintain asthma control. Asthma is an inflam-
matory condition. Thus, inhaled glucocorticosteroids are
currently the most effective antiinflammatory drug for the
treatment of persistent asthma.7,12 Glucocorticosteroids re-
duce asthma symptoms, improve lung function, decrease air-
way hyperreactivity, modulate airway inflammation, and re-
duce asthma exacerbations and asthma mortality.12 Inhaled
long-acting ␤2-agonists (formoterol, salmeterol) should
never be used as single therapy because these ␤2-agonists
improve lung function without antiinflammatory effects.12
Thus, significant clinical concerns regarding an increase in
asthma-related deaths in patients on long-acting ␤2-ago-
nists39 have led to revisions of product labels by the United
States Food and Drug Administration stating that long-act-
ing ␤2-agonists should never be used without concomitant
inhaled corticosteroid therapy.40 Thus, ␤2-agonists are most
efficient when combined with glucocorticosteroids, when in-
haled glucocorticosteroids alone fail to relieve asthma symp-
toms.7,12 Corticosteroids increase the bronchodilatory effect
of ␤2-agonists and increase the number of ␤2-adrenergic recep-
tors and their response to ␤2-agonists.41 In turn, rapid-acting
inhaled ␤2-agonists are used for quick relief of acute asthma
exacerbations.7,12 Additional studies are necessary to determine
whether tiotropium and possibly other long-acting anticholin-
ergic agents are effective and safe alternatives to long-acting ␤2-
agonists for the long-term treatment of asthma.42
# Association Française de Chirurgie & Société Française
d’Anesthésie et de Réanimation & Office Français de Prévention du
Tabagisme: Conférence d’Experts. Tabagisme péri-opératoire, 2005.
Available at: http://www.sfar.org/_docs/articles/151-Tabagisme%
20p%C3%A9riop%C3%A9ratoire-recommandations.pdf. Accessed
January 12, 2011.
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Bronchospasm during Anesthetic Induction
Preoperative Pulmonary Evaluation. In the presence of ac-
tive bronchospasm, elective surgery should be postponed.
The cause and corresponding clinical symptoms should be
actively treated until baseline status is achieved.3 Patients
should be free of wheezing, cough, or dyspnea.38 Individuals
having symptoms suggestive of asthma, outside the context
of an emergency situation, should undergo preoperative as-
sessment performed by pulmonologists to assess the degree of
airway reactivity and optimize preoperative treatment. Mea-
surement of lung function to prove airflow limitation and the
demonstration of reversibility of lung function abnormalities
enhance diagnostic confidence.12 Forced expiratory volume
in 1 s (FEV1) or peak expiratory flow (PEF) are valid mea-
sures of airway caliber and better indicators of the severity of
asthma exacerbation than clinical symptoms.7,12 FEV1 (nor-
mal is approximately 80 –100% of predicted) expressed as a
percentage of the vital capacity is the standard index for
assessing and quantifying airflow limitation. Reversibility
with the use of a bronchodilator is defined as an increase in
FEV1 of at least 12% or 200 ml. FEV1/forced vital capacity
(normal is greater than 75%) appears to be a more sensitive
measure of severity and control.7 In turn, a peak flow meter,
which measures the highest expiratory flow rate in liters of air
expired per second or per min (normal is greater than 80% of
predicted), is designed for monitoring due to the wide vari-
ability in reference values.7,12 Before surgery, PEF or FEV1
greater than 80% of the predicted or personal best is recom-
mended.38 If PEF or FEV1 is less than 80%, a brief course of
oral corticosteroids should be considered to reduce airflow
limitation.12 Patients with asthma who are also smokers have
poorer control of asthma.36 Abstinence from smoking before
surgery reduces perioperative pulmonary complications
rates. At least 2 months of preoperative cessation is required
to drastically reduce perioperative pulmonary complications
risk.38# A stepwise approach of either initiation or optimiza-
tion of asthma treatment according to the level of asthma was
proposed into either five12 or six steps7 reflecting increasing
intensity of treatment required to achieve asthma control
(table 1). Combined with educational and environmental
measures, therapy for asthma is subdivided into two catego-
ries (quick-relief and long-term control treatment). Briefly,
rapidly acting ␤2-agonist should be prescribed as needed at
each step. The first step concerns patients with occasional
daytime symptoms where rapid acting ␤2-agonist may be
sometimes requested. The second through fifth steps con-
cern a pattern of features involving partly controlled to se-
verely uncontrolled asthma where regular treatment is re-
quested. Low-dose inhaled corticosteroid is recommended
for the second step. The combination of a low-dose inhaled
corticosteroid with an inhaled long-acting ␤2-agonist or a
medium- or high-dose inhaled corticosteroid with an inhaled
long-acting ␤2-agonist is recommended for the third and
fourth steps, respectively. Oral corticosteroids may be useful
when added to other medications during the fifth step, which
concerns patients with frequent exacerbations and daily lim-
1206 Dewachter et al.
 EDUCATION
Table 1. Stepwise Approach for Asthma Treatment
Level of Asthma Control Step Levels
Global Initiative for Asthma 关12兴 Five
Intermittent treatment 1 —
Daily medication 2 Low-dose inhaled corticosteroid
— 3
— 4
— 5
Expert Panel Report 3 关7兴 Six
Intermittent treatment 1 —
Daily medication 2 Low-dose inhaled corticosteroid
— 3
— 4
— 5
— 6
itation of activities.12 The recommendations proposed in the
United States involve six steps but suggest a very similar
therapeutic strategy (table 1). Therapy is increased as neces-
sary and decreased when possible. In addition, some alterna-
tive drugs are also proposed. 7,12
A specific approach adapted to the preoperative stage,
including emergency and nonemergency conditions, was
proposed by a hospital-based working group.36 Thus, an
international consensus promoted by the different corre-
sponding anesthetic societies might be useful to define a
better approach to airway hyperreactivity during the periop-
erative period.
In the current case, secondary pulmonary assessment con-
firmed uncontrolled allergic asthma (dust mites, grass). Ini-
tial spirometric evaluation showed a reduction of FEV1 and
PEF at 67% and 70%, respectively, as well as an FEV1/forced
vitality capacity of 83% of predicted values. High doses of
inhaled therapy with fluticasone and salmeterol (1,000 ␮g,
twice per day) along with educative measures were initiated.
Three months later, a second spirometric evaluation showed
bronchospasm reversibility of nearly 15%, with FEV1 at
80%, PEF at 82%, and an FEV1/forced vitality capacity of
97% of predicted values along with reduction of clinical signs
noted by the patient as wheezing disappeared. These signif-
icant improvements have been noted at a constant body
weight. Surgery was performed 6 months after the initial
perioperative event. Anesthesia was conducted with propo-
fol, sufentanil, and sevoflurane. Anesthesia and surgery as
well as the postoperative course remained uneventful.
** British Thoracic Society & Scottish, Intercollegiate Guidelines
Network: British Guideline on the Management of Asthma: A Na-
tional Clinical Guideline. May 2008. Revised June 2009. Available at:
http://www.sign.ac.uk/pdf/sign101.pdf. Accessed January 12, 2011.
Anesthesiology 2011; 114:1200 –10
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Treatment
At each step, short-acting ␤2-agonist is recommended
as needed
Low-dose inhaled corticosteroid combined with an
inhaled long-acting ␤2-agonist
Medium- or high-dose inhaled glucocorticosteroid
with an inhaled long-acting ␤2-agonist
Addition of oral glucocorticosteroid to other controllers
At each step, short-acting ␤2-agonist is recommended
as needed
Medium-dose inhaled corticosteroid
Medium-dose inhaled corticosteroid combined with
an inhaled long-acting ␤2-agonist
High-dose inhaled corticosteroid combined with an
inhaled long-acting ␤2-agonist
High-dose inhaled corticosteroid combined with an
inhaled long-acting ␤2-agonist and oral corticosteroids
X. Treating Perioperative Bronchospasm
The aims of treatment are to relieve airflow obstruction and
subsequent hypoxemia as quickly as possible.
General Measures. When isolated perioperative broncho-
spasm occurs, oxygen concentration should be increased to
100%, and manual bag ventilation immediately started to
evaluate pulmonary compliance and to identify all causes of
high-circuit pressure.19 Increased concentration of a volatile
anesthetic (sevoflurane, isoflurane) is often useful3 with the
exception of desflurane because of its airway irritant effects,
particularly in smokers.43 Deepening anesthesia with an in-
travenous anesthetic (propofol) may be required because in-
tubation-induced bronchospasm may be related to an inad-
equate depth of anesthesia (fig. 3).
Inhaled Short-acting ␤2-Selective Agents Belong to Im-
mediate Therapy. Short-acting ␤2-selective agents (mainly
using terbutaline and salbutamol) are key drugs for the fast
relief of bronchoconstriction. Their onset of action occurs
within 5 min, peak effect is within 60 min, and duration of
action is 4 – 6 h. They should be immediately administered
via a nebulizer (8 –10 puffs to achieve appropriate therapeu-
tic levels, may be repeated at 15- to 30-min intervals) or, if
available, with a metered-dose inhaler (5–10 mg/h) con-
nected to the inspiratory limb of the ventilator circuit. There
is no difference in efficacy between terbutaline and salbuta-
mol.** Continuous rather than intermittent administration
of salbutamol results in greater improvement in PEF and
FEV1. Moreover, nebulized epinephrine has no beneficial
effect compared with terbutaline or salbutamol.**
Systemic Glucocorticosteroids Should Not be Omitted.
Parenteral steroids also remain a key drug in the treatment of
bronchospasm because they speed resolution of exacerba-
tions by decreasing airway inflammation. Systemic glucocor-
1207 Dewachter et al.
 Bronchospasm during Anesthetic Induction

Fig. 3. Stepwise approach to treatment of perioperative bronchospasm according to the clinical scenario. * May be used in
life-threatening bronchospasm or those with a poor initial response to ␤2-agonist; † may be used in cases of severe
bronchospasm that fails to relieve with ␤2-agonist; ‡ for further details, see Reference 1.

ticosteroids such as methylprednisone (1 mg 䡠 kg⫺1) are pre-
ferred over cortisone because their antiinflammatory effect is
more potent. However, the antiinflammatory benefit is not
immediate.
Alternative Agents. The use of an antimuscarinic inhaled
medication (e.g., ipratropium bromide) has been shown to
attenuate reflex-induced bronchoconstriction with efficacy
similar to inhaled ␤2-agonists.25 Thus, combined nebulized
ipratropium bromide (0.5 mg 4 – 6 times hourly) with a neb-
ulized ␤2-agonist produces greater bronchodilatation than a
␤2-agonist alone and may be used to treat life-threatening
bronchospasm or in those with a poor initial response to
␤2-agonist treatment.** Magnesium plays a beneficial role in
the treatment of asthma through bronchial smooth muscle
relaxation, leading to the use of intravenous (single dose of
magnesium sulfate: 2 g over 20 min) or inhaled preparations
(doses from 110 mg to 1,100 mg) in patients with severe
bronchospasm that fails to be relieved with ␤2-agonists.12**
Accordingly, salbutamol administered in isotonic magne-
sium sulfate provides greater benefit when compared with
that diluted with saline.12 Intravenous aminophylline has no
indication in acute bronchospasm because its use does not
result in additional bronchodilatation, whereas adverse ef-
fects such as arrhythmia and vomiting have been reported
when intravenous aminophylline was used.12**
Therapeutic Rationale for Epinephrine. Epinephrine should
be used in cases of associated cardiovascular collapse sugges-
tive of IgE-mediated anaphylaxis.1,12 During isolated bron-
chospasm, its inhaled/systemic use is not recommended be-
cause no study has proven its efficiency when compared with
␤2-agonists such as salbutamol or terbutaline12 and deleteri-
ous adverse effects, including takotsubo cardiomyopathy,
have been reported during asthma care.44 Others propose
systemic epinephrine but emphasize that no advantage has
been proven of systemic therapy over nebulization.7 Cur-
rently, no recommendations regarding epinephrine can be
proposed,45 except that its use would be reasonable as a rescue
therapy in patients with severe asthma complicated by hypoten-
sion that is not secondary to dynamic hyperinflation.46 Elective
surgery should be postponed unless bronchospasm persists at
baseline despite maximal medical optimization of the patient
and further care provided in a monitored setting.

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 EDUCATION
Table 2. Example of Targeting Questions to Identify
Patients at Risk with Undiagnosed Airway Hyperreactivity
Do you smoke?
Do you have gastroesophageal reflux disease?
Have you ever felt chest tightness or difficulty catching
your breath? If so, at rest or with physical effort?
Have you ever been told that you have wheezing or
asthma?
Have you ever used an inhaled medication for your
breathing?
Have you ever visited an emergency department for
breathing problems?
Have you ever had frequent bronchitis?
Have you ever had rhinitis?
Do you frequently cough?
Do you have allergies to latex or tropical fruits (kiwi,
banana, papaya, avocado)?
In our patient, extubation was performed because of
suspected esophageal intubation. Verification of correct
endotracheal tube position would have been the appropri-
ate procedure. The patient’s extubation was associated
with oxygen arterial desaturation and subsequent hemo-
dynamic disturbances.
XI. Knowledge Gap
Although factors contributing to airway inflammation in
asthma are multiple and not completely understood, factors
triggering perioperative bronchospasm are identified. Both
basic science and clinical research efforts could improve the
prevention and treatment of bronchospasm associated with
anesthesia. Clinical research leading to the prevention of
bronchospasm will require a better identification of patients
at risk and then a better classification of the phenotypes,
therapies, and level of control of asthma in patients during
the preoperative period. Nevertheless, it should be ques-
tioned whether perioperative bronchospasm is a clinical en-
tity of its own occurring in predisposed patients (e.g., asth-
matic patients and those with chronic obstructive pulmonary
disease or acute bronchitis) and triggered either by mechan-
ical, pharmacologic, or inflammatory (i.e., anaphylaxis) fac-
tors. Moreover, basic assumptions regarding the manage-
ment of general anesthesia in patients at risk for
bronchoconstriction have not been rigorously studied, spe-
cifically the assumption that intubation of the trachea carries
a higher risk of morbidity in the perioperative period com-
pared with airway devices such as the laryngeal mask airway.
Basic science advances are needed in the understanding of
the interaction between anesthetics, airway irritation, and
the role of tachykinins and other C fiber neurotransmitters in
the control of airway tone. Moreover, the mechanisms by
which intravenous and inhaled anesthetics affect airway
nerves and directly modulate airway smooth muscle tone
likely involve modulation of plasma membrane ion channels,
membrane potential, and intracellular calcium sensitivity but
remain poorly understood.
Anesthesiology 2011; 114:1200 –10
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An international consensus promoted by the different
corresponding anesthetic societies might be useful to define a
better approach of airway hyperreactivity as well as provide
key targeting questions to detect patients at risk during the
preoperative period (table 2) and propose clinical pathways.
The authors thank Sylvie Chollet-Martin, Pharm.D., Ph.D., Unité
d’Immunologie Auto-immunité & Hypersensibilités, Hôpital Bichat-
Claude Bernard, Assistance Publique Hôpitaux de Paris & Université
Paris-Sud 11, INSERM UMRS-996, Châtenay-Malabry, France, and
Pascale Nicaise-Roland, Pharm.D., Ph.D., Staff Biologist, Unité
d’Immunologie Auto-immunité & Hypersensibilités, Hôpital Bichat-
Claude Bernard, Paris, France, for performing biologic assessment
and Sylvie Bourdiau, M.D., Staff Anesthesiologist, Service
d’Anesthésie-Réanimation, Dominique Valeyre, M.D., Service de
Pneumologie, and Bruno Frachet, M.D., Service d’Oto-Rhino-Laryn-
gologie, Hôpital Avicenne, Assistance Publique Hôpitaux de Paris,
and Université Paris 13, Bobigny, France, for clinical management.
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