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Broncoespasmo durante induccion2011


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Broncoespasmo durante induccion2011

  1. 1. EDUCATION Bruno Riou, M.D., Ph.D., EditorCase Scenario: Bronchospasm during Anesthetic InductionPascale 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 tobecome an anesthetic disaster. During the perioperative pe- Case Report A 25-yr-old woman with morbid obesity (body mass index:riod, bronchospasm usually arises during induction of anes- 54 kg/m2) and noninsulin-dependent diabetes was sched-thesia but may also be detected at any stage of the anesthetic uled for cochlear implant surgery. She had two previous sur-course. Accordingly, prompt recognition and appropriate geries without incident during childhood. She denied anytreatment are crucial for an uneventful patient outcome. history of atopy or drug allergy. Chest auscultation was nor-Perioperative bronchospasm (i.e., the clinical expression of mal before anesthesia. She was premedicated with hy-exacerbated underlying airway reactivity) may be associated droxyzine (100 mg orally) the day before and 1 h beforewith type E immunoglobulin (IgE)-mediated anaphylaxis or anesthesia, which was induced with sufentanil (20 g intra-may occur as an independent clinical entity, triggered by venously) and propofol (350 mg intravenously). Trachealeither mechanical and/or pharmacologic factors. Whatever intubation (Cormack and Lehane grade I) was facilitatedthe clinical circumstances, different triggers are identified in with succinylcholine (130 mg intravenously). After trachealthe occurrence of perioperative bronchospasm with asthma, intubation was performed, chest auscultation revealed aa chronic inflammatory disorder of the airways frequently complete absence of bilateral breath sounds. Initial concen-involved. The purpose of this clinical scenario is to discuss trations of end-tidal carbon dioxide (ETCO2) were low. Be-the key points of perioperative bronchospasm. cause an esophageal intubation was suspected, the patient was immediately extubated and mask ventilation attempted. Mask ventilation was difficult to perform because of dramat- * Staff Anesthesiologist, Service d’Anesthesie-Reanimation and ´ ´ ically decreased lung compliance, whereas ETCO2 demon-SAMU de Paris, Universite Paris-Descartes, INSERM UMRS-970 and ´ strated a marked prolonged expiratory upstroke of the cap-Hopital Necker-Enfants Malades, Assistance Publique Hopitaux de ˆ ˆParis, Paris, France; † Staff Internist and Allergologist, Pole ˆ nogram. Therefore, bronchospasm was considered. Rapidd’Anesthesie-Reanimation Chirurgicale, CHU Hopital Central, ´ ´ ˆ arterial oxygen desaturation (oxygen saturation measured byNancy, France; ‡ Professor, Department of Anesthesiology, College pulse oximetry [SpO2], 55%) followed by arterial hypoten-of Physicians and Surgeons, Columbia University, New York, NewYork; § Professor, Service d’Anesthesie-Reanimation, Universite ´ ´ ´ sion (from 130/75 to 50/20 mmHg) associated with a mod-Paris 13 & Hopital Avicenne, Assistance Publique Hopitaux de Paris. ˆ ˆ erate tachycardia (100 beats/min) occurred in less than 5 min Received from the Universite Paris-Descartes, Paris, France. Sub- ´ after the onset of bronchospasm. Concomitantly, titratedmitted for publication August 28, 2010. Accepted for publication Feb- epinephrine (two intravenous boluses of 100 g each) alongruary 11, 2011. Support was provided solely from institutional and/ordepartmental sources. Figures 1–3 in this article were prepared by with fluid therapy with crystalloids (lactated Ringer’s solu-Annemarie B. Johnson, C.M.I., Medical Illustrator, Wake Forest Univer- tion, 1,000 ml) corrected the cardiovascular disturbances (ar-sity School of Medicine Creative Communications, Wake Forest Uni- terial blood pressure, 110/50 mmHg; heart rate, 110 beats/versity Medical Center, Winston-Salem, North Carolina. min) while at the same time ventilation became easier to Address correspondence to Dr. Dewachter: Serviced’Anesthesie-Reanimation & SAMU de Paris, Hopital Necker- ´ ´ ˆ perform along with the return of audible wheezing over bothEnfants Malades, 149 Rue de Sevres 75743 Paris Cedex 15, ` lung fields. As arterial blood pressure was restored, a localizedFrance. This article may be ac- (face and upper thorax) erythema occurred. Hydrocortisonecessed for personal use at no charge through the Journal Website, (200 mg) was intravenously administered. A blood sampleCopyright © 2011, the American Society of Anesthesiologists, Inc. Lippincott was obtained to measure serum tryptase concentrations, 40Williams & Wilkins. Anesthesiology 2011; 114:1200 –10 and 90 min after the clinical reaction. Surgery was post-Anesthesiology, V 114 • No 5 1200 May 2011
  2. 2. EDUCATIONponed, and the patient was transferred to the intensive care III. Etiology of This Perioperative Immediateunit. No additional supportive vasopressor therapy was re- Hypersensitivity in the Current Casequired. Respiratory symptoms resolved within 2 h after in- The sudden occurrence of bronchospasm after anesthetic in-haled 2-agonist (salbutamol; i.e., albuterol) and intravenous duction, with cardiovascular disturbances and cutaneouscorticoids (hydrocortisone, cumulative dose: 800 mg over signs, clinically suggested a drug-induced anaphylactic reac-24 h). Subsequent clinical outcome was uneventful, and the tion. Succinylcholine-induced anaphylaxis was the mostpatient was discharged home the following day and returned likely etiology, because neuromuscular blocking agents are6 weeks later for allergologic assessment (see section III). 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 solutionsDiscussion (Allerbio, Varennes en Argonne, France and Stallergenes, ` Antony, France). Tryptase levels (ImmunoCAP, PhadiaI. Diagnosis and Differential Diagnosis of Intraoperative SAS, Uppsala, Sweden) were unchanged (5.4 g l 1 andWheezing/Bronchospasm 4.3 g l 1; N less than 13.5 g l 1) in blood samplesBronchospasm encountered during the perioperative period obtained 40 and 90 min, respectively, after the onset of theand especially after induction/intubation may involve an im- reaction. Serum-specific IgEs (ImmunoCAP) against succi-mediate hypersensitivity reaction including IgE-mediated nylcholine and latex were not detectable. Specific serum IgEanaphylaxis or a nonallergic mechanism triggered by factors against quaternary ammonium was slightly increased (2.08such as mechanical (i.e., intubation-induced bronchospasm) kU/L, N less than 0.1). A basophil activation test was alsoor pharmacologic-induced (via histamine-releasing drugs performed and analyzed using a FACSCanto II flow cytom-such as atracurium or mivacurium) bronchoconstriction in eter (Becton-Dickinson, Rungis, France). Succinylcholinepatients with uncontrolled underlying airway hyperreactiv- induced neither CD63 nor CD203c up-regulation.ity.1,2 Chest auscultation should be done to confirm wheezing, Clinical Considerations. The chronology of evolving clinicalwhereas decreased or absent breath sounds suggest critically low features is crucial to understand the pathophysiologic mech-airflow.3 The differential diagnosis includes inadequate anesthe- anism of an immediate hypersensitivity reaction.sia, mucous plugging of the airway, esophageal intubation, Cardiovascular disturbance is the hallmark of severe IgE-kinked or obstructed tube/circuit, and pulmonary aspiration.3 mediated anaphylaxis. In patients with neuromuscularUnilateral wheezing suggests endobronchial intubation or an blocking agent-induced perioperative anaphylaxis, cardio-obstructed tube by a foreign body (such as a tooth).3 If the vascular signs are usually the inaugural clinical event andclinical symptoms fail to resolve despite appropriate therapy, occur within minutes after the drug challenge. These cardio-other etiologies such as pulmonary edema or pneumothorax vascular signs may be associated with or followed by bron-should also be considered. 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 occurII. Diagnosis of a Perioperative Immediate Reaction either before or after instrumentation of the airway2 (fig. 1).Immediate hypersensitivity is a clinical entity evoking allergy Latex-induced anaphylaxis typically occurs in patientsthat varies in severity1 and is subdivided into nonallergic with a history of atopy.6 Because atopy is the strongest iden-hypersensitivity (called anaphylactoid reaction by the Amer- tifiable predisposing factor for the development of asthma,7ican Academy of Allergy Asthma and Immunology) where an severe clinical features occurring during latex-induced ana-immune mechanism is excluded, and allergic hypersensitivity phylaxis usually involve cardiovascular signs followed by or(also called IgE-mediated anaphylaxis).4 By definition, im- associated with bronchospasm and cutaneous signs.8 As latexmediate hypersensitivity occurs within 60 min after the in- proteins are slowly absorbed, latex-induced anaphylaxis usu-jection/introduction of the culprit agent.1 The initial diag- ally occurs up to 30 – 60 min after the beginning of surgerynosis remains presumptive, whereas the etiologic diagnosis is (i.e., mucous membrane exposure).8linked to a triad including clinical features (the description of Acute increases in airway responsiveness may also occur inthe clinical features according to the adapted Ring and Mess- the absence of an antigen challenge and result from irritationmer clinical severity scale); blood tests (tryptase level mea- of the well-innervated upper airway by a foreign body (e.g.,surements, serum-specific IgEs); and postoperative skin tests endotracheal tube or suction catheter).2 Thus, nonallergicwith the suspected drugs or agents.1 bronchospasm immediately follows nonspecific stimuli and usually is not associated with cardiovascular symptoms2 (fig. 1). Grade I: Erythema, urticaria with or without angioedema; Nevertheless, positive end-expiratory pressure with severe bron-grade II: cutaneous-mucous signs hypotension tachycardia chospasm may lead to a decrease in venous return and hence ofdyspnea gastrointestinal disturbances; grade III: cardiovascular cardiac output. In addition, the association of hypoxia and re-collapse, tachycardia, or bradycardia cardiac dysrythmia broncho-spasm cutaneous-mucous signs gastrointestinal disturbances; spiratory failure from inadequate ventilation may lead tograde IV: cardiac arrest. cardiovascular collapse.9Anesthesiology 2011; 114:1200 –10 1201 Dewachter et al.
  3. 3. Bronchospasm during Anesthetic InductionFig. 1. Pathophysiologic mechanisms involved during perioperative immediate hypersensitivity reaction according to the onsetof bronchospasm when compared with endotracheal tube insertion.IV. Distinguishing the Pathophysiologic Mechanism of patients with isolated bronchospasm occurring after airwayPerioperative Bronchospasm Clinically instrumentation without an increase in tryptase. In the cur-Four clinical variables were identified as independent predic- rent case, allergic mast cell activation was ruled out becausetors of allergic compared with nonallergic perioperative tryptase levels measured within the recommended timebronchospasm: the presence of any cutaneous symptoms; frame remained unchanged. Skin tests were negative in re-shock; episodes of desaturation; and the prolonged duration sponse to the medications received (i.e., propofol, sufentanil,of clinical features (longer than 60 min).2 Compared with and succinylcholine) as well as latex. These results were cor-that of patients who did not present with these “predictive” roborated by basophil activation tests showing an absence ofsigns as part of the clinical syndrome, the occurrence of hy- CD63 and CD203c up-regulation with succinylcholine, rul-potension or episodes of oxygen desaturation were 27 and 21 ing out basophil sensitization by specific IgE toward succi-times, respectively, more likely to be associated with IgE- nylcholine and undetectable specific serum IgEs against suc-mediated anaphylaxis. In addition, symptom duration lon- cinylcholine. Serum IgEs against quaternary ammonium wasger than 60 min or the presence of skin changes was two and slightly increased (2.08 kU/L, N less than 0.1), but theseseven times, respectively, more likely to be associated with assays appear to be less sensitive than skin tests and do notIgE-mediated anaphylaxis.2 In the current case, inaugural prove that the drug/agent is responsible for the reaction.10severe bronchospasm triggered by endotracheal tube inser- Succinylcholine-induced anaphylaxis was therefore ruledtion and followed by cardiovascular collapse, likely related to out according to clinical, biologic, and allergologic evidence.subsequent hypoxemia after the patient’s extubation, yields This is of particular importance because succinylcholine isclinical insight into the pathophysiologic mechanism of the thereby allowed to be used for future anesthetics in this pa-reaction and suggests nonallergic bronchospasm. Cutaneous tient. In turn, uncontrolled asthma was suggested to be thesigns, such as erythema, are not specific for IgE-mediated main trigger of this nonallergic bronchospasm after endotra-anaphylaxis per se and may also be observed during nonaller- cheal tube insertion. Wheezing induced by bronchial infec-gic bronchospasm.2 The morbid obesity of the patient is tion during childhood or triggered by cold weather and ex-of clinical interest and could also have been a precipitating ercise in adulthood was elicited from the patient’s historyfactor of rapid arterial desaturation despite appropriate during the postoperative evaluation.preoxygenation.Allergologic Assessment: Blood Tests and Skin Testing. A V. Asthma Is a Frequently Underdiagnosed Conditiontryptase increase is specific for mast cell activation such as Asthma is one of the most common chronic airway diseasesthat occurring during IgE-mediated anaphylaxis.1 Increased worldwide, with a higher prevalence and incidence in thetryptase levels appear to distinguish clearly between allergic Western world.11 The estimated annual death rate world-and nonallergic perioperative bronchospasm.2 Thus, Fisher2 wide is 250,000.12 However, this condition frequently re-suggested that an allergologic assessment is unnecessary in mains underdiagnosed. In 2008, the following definition forAnesthesiology 2011; 114:1200 –10 1202 Dewachter et al.
  4. 4. EDUCATIONasthma was suggested: “Asthma is a chronic disorder of the characterized by nasal symptoms including sneezing, nasalairway in which many cells and cellular elements play a role. The blockage, and/or itching of the nose; is either intermittent orchronic inflammation is associated with airway responsiveness permanent; and is classified as mild, moderate, or severe.15that leads to recurrent episodes of wheezing, breathlessness, chest More than 80% of asthmatic individuals have rhinitis, andtightness and coughing, particularly at night or in the early 10 – 40% of patients with rhinitis have asthma. A combinedmorning. These episodes are usually associated with widespread, strategy should ideally be used to treat the upper and lowerbut variable airflow obstruction within the lung, that is often airway diseases (allergen avoidance is crucial but inhaled/reversible either spontaneously or with treatment.”12 This pro- intranasal corticosteroid is the most consistently effectiveposal was ratified in the United States.7 Accordingly, a Eu- long-term control therapy attenuating airway inflamma-ropean and American Task Force issued by the correspond- tion). 7,15 Because the presence of asthma must be considereding Respiratory Societies suggested that the definition of in all patients with rhinitis, those with severe and/or persis-asthma includes two domains (symptoms and variable airway tent uncontrolled allergic rhinitis should be evaluated forobstruction) being assessed in clinical practice, with two ad- asthma before surgery.ditional domains (airway inflammation and hyperrespon- Nonallergic Asthma: Aspirin-induced Asthma. The othersiveness) characterizing the underlying disease. An individual main variant of asthma in adults includes a widely underdi-may have features of any or all of these domains.13 Airway agnosed phenotype not seen in childhood, such as aspirin-hyperresponsiveness is induced by a variety of changes in the induced asthma. Aspirin-induced asthma is characterized byairway and sustained by underlying airway inflammation, the eosinophilic rhinosinusitis, nasal polyposis, aspirin or non-hallmark of asthma. steroidal antiinflammatory drug sensitivity, and asthma. Recently, a crucial modification in the approach to Asthma and sensitivity to aspirin usually appear approxi-asthma management was proposed with a classification by mately 1–5 yr after the onset of rhinitis,16 whereas rhinor-the level of asthma control (controlled, partly controlled, or rhea, nasal congestion, and anosmia are usually the first clin-uncontrolled) rather than asthma severity per se while linking ical features of aspirin-induced asthma. This phenotypethe classification of asthma control to asthma treatment.12 results from the inhibition of cyclooxygenase enzymes byTwo Main Phenotypes of Asthma Can be Distinguished. aspirin-like drugs in the airway of sensitive patients and is notTwo main phenotypes of asthma, allergic and nonallergic, sustained by an allergic mechanism.16are most commonly discussed; overlap may occur withinthese groups.14 VI. Perioperative BronchospasmAllergic Asthma. The largest overall phenotype in children Asthma is considered to be more prevalent in westernizedand adults is allergic asthma. Although allergic asthma is a countries.11 Surprisingly, no academic society of anesthesi-chronic and often lifelong disease, its onset occurs primarily ology issued from the European or the North American con-in early childhood. However, more than 50% of asthma is tinents has published recommendations concerning the peri-allergic in adults.4 It results from immunologic reactions, operative management of the asthmatic patient. Themostly initiated by IgE antibodies, and is also called IgE- literature on this topic remains scarce.mediated allergic asthma. Genetic factors may promote the Epidemiology of Perioperative Bronchospasm. The occur-development of allergic asthma (inheritable component). rence of perioperative bronchospasm has been reported in upEnvironmental factors such as tobacco smoke, air pollutants, to 9% of asthmatic patients given general anesthesia, mainlyand exposure to allergens including indoor (mites, animals, after endotracheal tube insertion.17 Smoking also representsplant origin, e.g., ficus), outdoor (pollens, molds) or occupa- a major risk. Compared with that of nonsmokers, the relativetional allergens may trigger asthma. Obesity, diet, and a hy- risk of perioperative bronchospasm in smokers appearsgiene hypothesis may also trigger asthma.11 Thus, any poten- higher in females and in young smokers (16 –39 yrs old) andtial risk factor must eventually interact with an underlying is higher in patients with chronic bronchitis than in asymp-genetically determined pathway to result in the manifesta- tomatic patients.18tion of disease (epigenetic component). However, atopy, the Why and When Does Perioperative Bronchospasm Occur?genetic predisposition for the development of an IgE-medi- Of the 4,000 incidents reported in Australia, 103 reports ofated response to common aeroallergens, is the strongest iden- perioperative bronchospasm (3%) showed that an allergictifiable predisposing factor for developing asthma.7 Two ma- mechanism was less frequently involved (21%) than a non-jor factors such as airborne allergens and viral respiratory allergic mechanism (79%).19 Among these nonallergic cases,infections seem to be the most important in the develop- 44% occurred during the induction of anesthesia, 36% dur-ment, persistence, and possibly the severity of allergic ing the maintenance phase, and 20% during the emergence/asthma.7 recovery stage. During induction of anesthesia, broncho-Allergic Rhinitis and Allergic Asthma Belong to the Same spasm was mainly related to airway irritation (64%), whereasAirway Disease. The effect of allergic rhinitis on asthma remaining causes were due to tube misplacement (17%),should also be highlighted15 because the link of this distur- aspiration (11%), and other pulmonary edema or unknownbance with asthma remains poorly understood. Rhinitis is causes (8%). During the maintenance stage of anesthesia,Anesthesiology 2011; 114:1200 –10 1203 Dewachter et al.
  5. 5. Bronchospasm during Anesthetic Inductionallergy (34%), endotracheal tube malposition (23%), airway onto airway structures, most prominently the M3 muscarinicirritation (11%), and aspiration with a laryngeal mask airway receptor on airway smooth muscle that induces airway con-(9%) together accounted for almost 80% of the occurrences striction.24 Thus, the initial airway irritant stimulus sends anof bronchospasm. During induction or maintenance of an- afferent signal to the brainstem, resulting in an efferent signalesthesia, bronchospasm caused by airway irritation occurred traveling in the vagus and releasing acetylcholine in the air-more frequently in patients who had one or more predispos- way (fig. 2). Because acetylcholine acting on M3 muscarinicing factors such as asthma, heavy smoking, or bronchitis. receptors on airway smooth muscle is a key mechanistic com-Others showed that an allergic mechanism accounted for ponent of reflex-induced bronchoconstriction, the use of an-60% of the cases in patients experiencing bronchospasm dur- timuscarinic-inhaled medications (e.g., ipratropium oring induction of anesthesia.2 A previous history of asthma tiotropium) should be advantageous to prevent or treat thiswas present in 50% and 60% of patients with nonallergic and phenomenon.25 In addition, nonadrenergic noncholinergicallergic bronchospasm, respectively. Thus, uncontrolled nerves releasing tachykinins, vasoactive intestinal peptide,asthma/chronic obstructive pulmonary disease is frequently and calcitonin gene-related peptide may participate in thisinvolved with either pathophysiologic mechanisms (allergic reflex arc and/or locally release the procontractile neurotrans-vs. nonallergic), regardless of the stage of anesthesia (induc- mitters via activation of interneurons in the airway.26 A re-tion or maintenance). cent study suggests that propofol preferentially relaxes tachy-Morbidity and Mortality Rates. Respiratory events ac- kinin-induced airway constriction in airway smoothcounted for 28% of claims concerning anesthesia-related muscle.27 It has long been clinically recognized that thebrain damage and death in the United States.20 In this series, depth of anesthesia modulates the likelihood of eliciting re-bronchospasm was included in the other categories and to- flex-induced bronchoconstriction, but the pharmacologicgether corresponded to 11% of total respiratory events. In mechanisms by which this occurs are unknown. Propofol28the United Kingdom, respiratory and airway incidents ac- and the volatile inhalational anesthetics (with the exceptioncounted for 3% and 8%, respectively, of all claims including of desflurane) are known to be clinically effective at prevent-severe and fatal outcomes.21 Bronchospasm was not detailed. ing reflex-induced bronchoconstriction or attenuating intra-Nevertheless, airway incidents belong to the claims with the operative bronchoconstriction.29 These agents share activityhighest overall cost and respiratory complications with the at inhibitory -aminobutyric acid-A chloride channels30;highest mean cost per closed claim. Seven percent of anes- thus, it has been speculated that modulation of -aminobu-thesia-related deaths were attributed to bronchospasm in tyric acid input to the airway-related vagal preganglionicFrance.22 neurons from the nucleus of the solitary tract and higher In conclusion, bronchospasm remains a serious life- central nervous system centers may be a mechanism by whichthreatening perioperative event. Its dramatic consequences deepening anesthesia prevents or relieves reflex-inducedinvolving brain damage or death may be partly explained by bronchoconstriction. Moreover, both propofol and inhala-substandard care and/or inadequate practice and system fail- tional anesthetics have direct bronchodilatory effects at theures.20,22 Optimal management of perioperative broncho- level of airway smooth muscle itself 31 acting via -aminobu-spasm should therefore be encouraged through teaching ap- tyric acid-A channels32 or modulating calcium sensitivity ofplications such as an anesthesia simulator to compensate for the contractile proteins.33 However, despite these protectivethe low frequency with which the average practitioner would effects of intravenous propofol and the adequate inductionencounter severe bronchospasm during routine clinical care. dose used in the current case, reflex-induced bronchocon-Basic Science: Mechanisms of Reflex-induced Broncho- striction developed in this patient who had previously unrec-constriction. The mechanisms of asthmatic exacerbations ognized and untreated asthma.resulting in bronchoconstriction are complex and involveairway nerves, smooth muscle, epithelium, and inflamma- VII. Obesity and Asthma: Is There Any Relationship?tory cells. However, reflex-induced bronchoconstriction in- There is increasing evidence linking obesity, defined as aduced by irritation of the upper airway by a foreign body body mass index of at least 30 kg/m2, to asthma and airwaysuch as an endotracheal tube is modulated by synapse of hyperreactivity in both children and adults.34 Both asthmaafferent sensory pathways in the nucleus of the solitary tract, and obesity are systemic inflammatory states. Their develop-which projects to the airway-related vagal preganglionic neu- ment seems to be determined early in life, with this associa-rons. The excitatory neurotransmitter glutamate modulates tion not being mediated through atopy.34 In turn, potentialstimulation of the nucleus of the solitary tract and airway- explanations for the parallel increase of asthma and obesityrelated vagal preganglionic neurons, whereas inhibitory might involve genetic, mechanical, hormonal, and environ-nerves releasing -aminobutyric acid project from the nu- mental factors. Accordingly, chromosomal regions with locicleus of the solitary tract to the airway-related vagal pregan- common to obesity and asthma phenotypes have been iden-glionic neurons.23 The excitatory outflow from the airway- tified. Reduced functional residual capacity and decreasedrelated vagal preganglionic neurons back to the airway is tidal volume as a result of obesity result in greater contractilecarried in the vagus nerve and results in acetylcholine release responses of airway smooth muscle, causing potentially in-Anesthesiology 2011; 114:1200 –10 1204 Dewachter et al.
  6. 6. EDUCATIONFig. 2. Schematic diagram of airway irritant reflex-induced bronchoconstriction by tracheal intubation. The upper airway is wellinnervated by afferent sensory pathways synapsing in the nucleus of the solitary tract (nTS), which projects excitatoryglutaminergic 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 muscarinicreceptors on airway smooth muscle inducing bronchoconstriction.creased airway reactivity.34 –35 Although gastroesophageal re- In the current case and after the clinical postanestheticflux resulting from obesity may potentially trigger a latent evaluation, borderline sleep-disordered breathing was alsoasthmatic condition,11 this condition was ruled out with an detected through polysomnography.esophageal transit test. Hormonal influences may also be involved as the effect of IX. Prevention of Perioperative Bronchospasmobesity on asthma is stronger in females than males.35 In The controls of airway inflammation and corresponding asthmaaddition, the hormone leptin produced by adipocytes and symptoms are essential to optimize perioperative and postoper-that acts in the hypothalamus to signal satiety35 has effects on ative care. The National Asthma Education and Preventionimmune cell function and inflammation. Serum leptin levels Program Expert Panel Report 3 recommends that the level ofin adulthood were shown to be higher in women than men asthma control, medication use (especially oral systemic corti-with a higher prevalence of asthma.34 The association be- costeroid within the past 6 months), and pulmonary functiontween asthma and obesity may be of recent origin, suggesting be reviewed before surgery.7 The Global Initiative for Asthmathat recent changes in lifestyle and diet are now associated guidelines suggest that perioperative and postoperative compli-with both asthma and obesity.11 However, weight gain an- cations rely on the severity of asthma at the time of surgery, thetedates asthma or asthma symptoms, ruling out the hypoth- type of surgery (thoracic and upper abdominal surgeries being atesis that this association might be the result of reduced phys- increased risk), and modalities of anesthesia (general anesthesiaical activity by asthmatic patients leading to obesity.34 with tracheal intubation is at higher risk).12 Others suggest that uncontrolled or poorly controlled asthma may be assessedVIII. Sleep-disordered Breathing and Asthma through the degree of asthma control (increased use of inhaledSleep-disordered breathing is more prevalent in asthmatic short-acting 2-agonists, previous/current use of inhaled corti-individuals than in those without asthma, whereas sleep- costeroids, recent use of oral/injected corticosteroids, recent ex-disordered breathing and asthma share common risk factors acerbations of asthma symptoms, emergency department orsuch as obesity.35 The reasons for the association between hospital visit within the last months) and potential risks or com-both conditions remain unknown.35 Asthma remains under- plication factors (recent infection of the respiratory tract, previ-diagnosed in obese patients because respiratory symptoms ous bronchospasm after intubation, pulmonary complicationsare frequently attributed to being overweight, as was the case during/after previous surgical procedure, long-term use of a sys-in our patient. In such patients, underlying airway hyperre- temic corticosteroid for severe asthma, associated gastroesopha-activity should be cautiously assessed during the preoperative geal reflux or smoking).36 The common key point of these rec-evaluation (see section IX). ommendations focuses on the level of asthma control beforeAnesthesiology 2011; 114:1200 –10 1205 Dewachter et al.
  7. 7. Bronchospasm during Anesthetic Inductionsurgery7,12,36 as uncontrolled asthma is considered to be the Preoperative Pulmonary Evaluation. In the presence of ac-main risk factor for bronchoconstriction during surgery.36 tive bronchospasm, elective surgery should be postponed.Preoperative Clinical and Physical Examination. Careful The cause and corresponding clinical symptoms should beclinical and physical examinations are therefore crucial for actively treated until baseline status is achieved.3 Patientspreoperative pulmonary risk assessment to identify findings should be free of wheezing, cough, or dyspnea.38 Individualssuggestive of unrecognized underlying airway hyperreactiv- having symptoms suggestive of asthma, outside the contextity. Decreased breath sounds as seen in markedly decreased of an emergency situation, should undergo preoperative as-expiratory airflow, sibilants, rhonchi, and prolonged expira- sessment performed by pulmonologists to assess the degree oftory phase, as well as recent and/or frequent exacerbations of airway reactivity and optimize preoperative treatment. Mea-respiratory symptoms including wheezing, cough, exercise surement of lung function to prove airflow limitation and theintolerance, unexplained dyspnea, and gastroesophageal re- demonstration of reversibility of lung function abnormalitiesflux disease should raise concern during the preoperative enhance diagnostic confidence.12 Forced expiratory volumeevaluation.3 Among these different findings, decreased in 1 s (FEV1) or peak expiratory flow (PEF) are valid mea-breath sounds, dullness to percussion, wheezing, rhonchi, sures of airway caliber and better indicators of the severity ofand a prolonged expiratory phase predict an increase in the asthma exacerbation than clinical symptoms.7,12 FEV1 (nor-risk of perioperative pulmonary complications.37 Thus, poorly mal is approximately 80 –100% of predicted) expressed as acontrolled asthma usually favors perioperative pulmonary com- percentage of the vital capacity is the standard index forplications3,36,38 whereas airway instrumentation may induce assessing and quantifying airflow limitation. Reversibilitylife-threatening bronchospasm, perioperative complications, with the use of a bronchodilator is defined as an increase inand prolonged intensive care treatment.20 Conversely, con- FEV1 of at least 12% or 200 ml. FEV1/forced vital capacitytrolled asthma does not promote additional risk.36,38 (normal is greater than 75%) appears to be a more sensitiveCorticosteroids Are the Key Point of Antiasthma Long- measure of severity and control.7 In turn, a peak flow meter,term Control Therapy. Long-term therapy is used daily to which measures the highest expiratory flow rate in liters of airachieve and maintain asthma control. Asthma is an inflam- expired per second or per min (normal is greater than 80% ofmatory condition. Thus, inhaled glucocorticosteroids are predicted), is designed for monitoring due to the wide vari-currently the most effective antiinflammatory drug for the ability in reference values.7,12 Before surgery, PEF or FEV1treatment of persistent asthma.7,12 Glucocorticosteroids re- greater than 80% of the predicted or personal best is recom-duce asthma symptoms, improve lung function, decrease air- mended.38 If PEF or FEV1 is less than 80%, a brief course ofway hyperreactivity, modulate airway inflammation, and re- oral corticosteroids should be considered to reduce airflowduce asthma exacerbations and asthma mortality.12 Inhaled limitation.12 Patients with asthma who are also smokers havelong-acting 2-agonists (formoterol, salmeterol) should poorer control of asthma.36 Abstinence from smoking beforenever be used as single therapy because these 2-agonists surgery reduces perioperative pulmonary complicationsimprove lung function without antiinflammatory effects.12 rates. At least 2 months of preoperative cessation is required to drastically reduce perioperative pulmonary complicationsThus, significant clinical concerns regarding an increase in risk.38# A stepwise approach of either initiation or optimiza-asthma-related deaths in patients on long-acting 2-ago- tion of asthma treatment according to the level of asthma wasnists39 have led to revisions of product labels by the United proposed into either five12 or six steps7 reflecting increasingStates Food and Drug Administration stating that long-act- intensity of treatment required to achieve asthma controling 2-agonists should never be used without concomitant (table 1). Combined with educational and environmentalinhaled corticosteroid therapy.40 Thus, 2-agonists are most measures, therapy for asthma is subdivided into two catego-efficient when combined with glucocorticosteroids, when in- ries (quick-relief and long-term control treatment). Briefly,haled glucocorticosteroids alone fail to relieve asthma symp- rapidly acting 2-agonist should be prescribed as needed attoms.7,12 Corticosteroids increase the bronchodilatory effect each step. The first step concerns patients with occasionalof 2-agonists and increase the number of 2-adrenergic recep- daytime symptoms where rapid acting 2-agonist may betors and their response to 2-agonists.41 In turn, rapid-acting sometimes requested. The second through fifth steps con-inhaled 2-agonists are used for quick relief of acute asthma cern a pattern of features involving partly controlled to se-exacerbations.7,12 Additional studies are necessary to determine verely uncontrolled asthma where regular treatment is re-whether tiotropium and possibly other long-acting anticholin- quested. Low-dose inhaled corticosteroid is recommendedergic agents are effective and safe alternatives to long-acting 2- for the second step. The combination of a low-dose inhaledagonists for the long-term treatment of asthma.42 corticosteroid with an inhaled long-acting 2-agonist or a # Association Francaise de Chirurgie & Societe Francaise ¸ ´ ´ ¸ medium- or high-dose inhaled corticosteroid with an inhaledd’Anesthesie et de Reanimation & Office Francais de Prevention du ´ ´ ¸ ´ long-acting 2-agonist is recommended for the third andTabagisme: Conference d’Experts. Tabagisme peri-operatoire, 2005. ´ ´ ´ fourth steps, respectively. Oral corticosteroids may be usefulAvailable at: Accessed when added to other medications during the fifth step, whichJanuary 12, 2011. concerns patients with frequent exacerbations and daily lim-Anesthesiology 2011; 114:1200 –10 1206 Dewachter et al.
  8. 8. EDUCATIONTable 1. Stepwise Approach for Asthma Treatment Level of Asthma Control Step Levels TreatmentGlobal Initiative for Asthma 12 Five At each step, short-acting 2 -agonist is recommended as needed Intermittent treatment 1 — Daily medication 2 Low-dose inhaled corticosteroid — 3 Low-dose inhaled corticosteroid combined with an inhaled long-acting 2-agonist — 4 Medium- or high-dose inhaled glucocorticosteroid with an inhaled long-acting 2-agonist — 5 Addition of oral glucocorticosteroid to other controllersExpert Panel Report 3 7 Six At each step, short-acting 2-agonist is recommended as needed Intermittent treatment 1 — Daily medication 2 Low-dose inhaled corticosteroid — 3 Medium-dose inhaled corticosteroid — 4 Medium-dose inhaled corticosteroid combined with an inhaled long-acting 2-agonist — 5 High-dose inhaled corticosteroid combined with an inhaled long-acting 2-agonist — 6 High-dose inhaled corticosteroid combined with an inhaled long-acting 2-agonist and oral corticosteroidsitation of activities.12 The recommendations proposed in the X. Treating Perioperative BronchospasmUnited States involve six steps but suggest a very similar The aims of treatment are to relieve airflow obstruction andtherapeutic strategy (table 1). Therapy is increased as neces- subsequent hypoxemia as quickly as possible.sary and decreased when possible. In addition, some alterna- General Measures. When isolated perioperative broncho-tive drugs are also proposed. 7,12 spasm occurs, oxygen concentration should be increased to A specific approach adapted to the preoperative stage, 100%, and manual bag ventilation immediately started toincluding emergency and nonemergency conditions, was evaluate pulmonary compliance and to identify all causes ofproposed by a hospital-based working group.36 Thus, an high-circuit pressure.19 Increased concentration of a volatileinternational consensus promoted by the different corre- anesthetic (sevoflurane, isoflurane) is often useful3 with thesponding anesthetic societies might be useful to define a exception of desflurane because of its airway irritant effects,better approach to airway hyperreactivity during the periop- particularly in smokers.43 Deepening anesthesia with an in-erative period. travenous anesthetic (propofol) may be required because in- In the current case, secondary pulmonary assessment con- tubation-induced bronchospasm may be related to an inad-firmed uncontrolled allergic asthma (dust mites, grass). Ini- equate depth of anesthesia (fig. 3).tial spirometric evaluation showed a reduction of FEV1 and Inhaled Short-acting 2-Selective Agents Belong to Im-PEF at 67% and 70%, respectively, as well as an FEV1/forced mediate Therapy. Short-acting 2-selective agents (mainlyvitality capacity of 83% of predicted values. High doses of using terbutaline and salbutamol) are key drugs for the fastinhaled therapy with fluticasone and salmeterol (1,000 g, relief of bronchoconstriction. Their onset of action occurstwice per day) along with educative measures were initiated. within 5 min, peak effect is within 60 min, and duration ofThree months later, a second spirometric evaluation showed action is 4 – 6 h. They should be immediately administeredbronchospasm reversibility of nearly 15%, with FEV1 at via a nebulizer (8 –10 puffs to achieve appropriate therapeu-80%, PEF at 82%, and an FEV1/forced vitality capacity of tic levels, may be repeated at 15- to 30-min intervals) or, if97% of predicted values along with reduction of clinical signs available, with a metered-dose inhaler (5–10 mg/h) con-noted by the patient as wheezing disappeared. These signif- nected to the inspiratory limb of the ventilator circuit. Thereicant improvements have been noted at a constant body is no difference in efficacy between terbutaline and salbuta-weight. Surgery was performed 6 months after the initial mol.** Continuous rather than intermittent administrationperioperative event. Anesthesia was conducted with propo- of salbutamol results in greater improvement in PEF andfol, sufentanil, and sevoflurane. Anesthesia and surgery as FEV1. Moreover, nebulized epinephrine has no beneficialwell as the postoperative course remained uneventful. effect compared with terbutaline or salbutamol.** Systemic Glucocorticosteroids Should Not be Omitted. ** British Thoracic Society & Scottish, Intercollegiate Guidelines Parenteral steroids also remain a key drug in the treatment ofNetwork: British Guideline on the Management of Asthma: A Na-tional Clinical Guideline. May 2008. Revised June 2009. Available at: bronchospasm because they speed resolution of exacerba- Accessed January 12, 2011. tions by decreasing airway inflammation. Systemic glucocor-Anesthesiology 2011; 114:1200 –10 1207 Dewachter et al.
  9. 9. Bronchospasm during Anesthetic InductionFig. 3. Stepwise approach to treatment of perioperative bronchospasm according to the clinical scenario. * May be used inlife-threatening bronchospasm or those with a poor initial response to 2-agonist; † may be used in cases of severebronchospasm that fails to relieve with 2-agonist; ‡ for further details, see Reference 1.ticosteroids such as methylprednisone (1 mg kg 1) are pre- indication in acute bronchospasm because its use does notferred over cortisone because their antiinflammatory effect is result in additional bronchodilatation, whereas adverse ef-more potent. However, the antiinflammatory benefit is not fects such as arrhythmia and vomiting have been reportedimmediate. when intravenous aminophylline was used.12**Alternative Agents. The use of an antimuscarinic inhaled Therapeutic Rationale for Epinephrine. Epinephrine shouldmedication (e.g., ipratropium bromide) has been shown to be used in cases of associated cardiovascular collapse sugges-attenuate reflex-induced bronchoconstriction with efficacy tive of IgE-mediated anaphylaxis.1,12 During isolated bron-similar to inhaled 2-agonists.25 Thus, combined nebulized chospasm, its inhaled/systemic use is not recommended be-ipratropium bromide (0.5 mg 4 – 6 times hourly) with a neb- cause no study has proven its efficiency when compared with 12ulized 2-agonist produces greater bronchodilatation than a 2-agonists such as salbutamol or terbutaline and deleteri- 2-agonist alone and may be used to treat life-threatening ous adverse effects, including takotsubo cardiomyopathy,bronchospasm or in those with a poor initial response to have been reported during asthma care.44 Others propose 2-agonist treatment.** Magnesium plays a beneficial role in systemic epinephrine but emphasize that no advantage hasthe treatment of asthma through bronchial smooth muscle been proven of systemic therapy over nebulization.7 Cur-relaxation, leading to the use of intravenous (single dose of rently, no recommendations regarding epinephrine can bemagnesium sulfate: 2 g over 20 min) or inhaled preparations proposed,45 except that its use would be reasonable as a rescue(doses from 110 mg to 1,100 mg) in patients with severe therapy in patients with severe asthma complicated by hypoten-bronchospasm that fails to be relieved with 2-agonists.12** sion that is not secondary to dynamic hyperinflation.46 ElectiveAccordingly, salbutamol administered in isotonic magne- surgery should be postponed unless bronchospasm persists atsium sulfate provides greater benefit when compared with baseline despite maximal medical optimization of the patientthat diluted with saline.12 Intravenous aminophylline has no and further care provided in a monitored setting.Anesthesiology 2011; 114:1200 –10 1208 Dewachter et al.
  10. 10. EDUCATIONTable 2. Example of Targeting Questions to Identify An international consensus promoted by the differentPatients at Risk with Undiagnosed Airway Hyperreactivity corresponding anesthetic societies might be useful to define a better approach of airway hyperreactivity as well as provideDo you smoke?Do you have gastroesophageal reflux disease? key targeting questions to detect patients at risk during theHave you ever felt chest tightness or difficulty catching preoperative period (table 2) and propose clinical pathways. your breath? If so, at rest or with physical effort?Have you ever been told that you have wheezing or The authors thank Sylvie Chollet-Martin, Pharm.D., Ph.D., Unite ´ asthma? d’Immunologie Auto-immunite & Hypersensibilites, Hopital Bichat- ´ ´ ˆHave you ever used an inhaled medication for your Claude Bernard, Assistance Publique Hopitaux de Paris & Universite ˆ ´ Paris-Sud 11, INSERM UMRS-996, Chatenay-Malabry, France, and ˆ breathing? Pascale Nicaise-Roland, Pharm.D., Ph.D., Staff Biologist, Unite ´Have you ever visited an emergency department for d’Immunologie Auto-immunite & Hypersensibilites, Hopital Bichat- ´ ´ ˆ breathing problems? Claude Bernard, Paris, France, for performing biologic assessmentHave you ever had frequent bronchitis? and Sylvie Bourdiau, M.D., Staff Anesthesiologist, ServiceHave you ever had rhinitis? d’Anesthesie-Reanimation, Dominique Valeyre, M.D., Service de ´ ´Do you frequently cough? Pneumologie, and Bruno Frachet, M.D., Service d’Oto-Rhino-Laryn-Do you have allergies to latex or tropical fruits (kiwi, gologie, Hopital Avicenne, Assistance Publique Hopitaux de Paris, ˆ ˆ and Universite Paris 13, Bobigny, France, for clinical management. ´ banana, papaya, avocado)? References In our patient, extubation was performed because of 1. Dewachter P, Mouton-Faivre C, Emala CW: Anaphylaxis andsuspected esophageal intubation. Verification of correct anesthesia: Controversies and new insights. ANESTHESIOLOGY 2009; 111:1141–50endotracheal tube position would have been the appropri- 2. Fisher MM, Ramakrishnan N, Doig G, Rose M, Baldo B: Theate procedure. The patient’s extubation was associated investigation of bronchospasm during induction of anaesthe-with oxygen arterial desaturation and subsequent hemo- sia. Acta Anaesthesiol Scand 2009; 53:1006 –11dynamic disturbances. 3. Woods BD, Sladen RN: Perioperative considerations for the patient with asthma and bronchospasm. Br J Anaesth 2009; 103(Suppl 1):i57– 65XI. Knowledge Gap 4. Johansson SG, Bieber T, Dahl R, Friedmann PS, Lanier BQ,Although factors contributing to airway inflammation in Lockey RF, Motala C, Ortega Martell JA, Platts-Mills TA, Ring J, Thien F, Van Cauwenberge P, Williams HC: Revised no-asthma are multiple and not completely understood, factors menclature for allergy for global use: Report of the Nomen-triggering perioperative bronchospasm are identified. Both clature Review Committee of the World Allergy Organiza-basic science and clinical research efforts could improve the tion, October 2003. J Allergy Clin Immunol 2004; 113:832– 6prevention and treatment of bronchospasm associated with 5. Hepner DL, Castells MC: Anaphylaxis during the periopera- tive period. Anesth Analg 2003; 97:1381–95anesthesia. Clinical research leading to the prevention of 6. Sampathi V, Lerman J: Perioperative latex allergy in children.bronchospasm will require a better identification of patients ANESTHESIOLOGY 2011; 114:673– 80at risk and then a better classification of the phenotypes, 7. National Asthma Education and Prevention Program Experttherapies, and level of control of asthma in patients during Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clinthe preoperative period. Nevertheless, it should be ques- Immunol 2007; 120:S94 –138tioned whether perioperative bronchospasm is a clinical en- 8. Hepner DL, Castells MC: Latex allergy: An update. Anesthtity of its own occurring in predisposed patients (e.g., asth- Analg 2003; 96:1219 –29matic patients and those with chronic obstructive pulmonary 9. Hepner DL: Sudden bronchospasm on intubation: Latex ana- phylaxis? J Clin Anesth 2000; 12:162– 6disease or acute bronchitis) and triggered either by mechan- 10. Harper NJ, Dixon T, Dugue P, Edgar DM, Fay A, Gooi HC, ´ical, pharmacologic, or inflammatory (i.e., anaphylaxis) fac- Herriot R, Hopkins P, Hunter JM, Mirakian R, Pumphrey RS,tors. Moreover, basic assumptions regarding the manage- Seneviratne SL, Walls AF, Williams P, Wildsmith JA, Wood P,ment of general anesthesia in patients at risk for Nasser AS, Powell RK, Mirakhur R, Soar J: Working Party of the Association of Anaesthetists of Great Britain and Ireland:bronchoconstriction have not been rigorously studied, spe- Suspected anaphylactic reactions associated with anaesthe-cifically the assumption that intubation of the trachea carries sia. Anaesthesia 2009; 64:199 –211a higher risk of morbidity in the perioperative period com- 11. Eder W, Ege MJ, von Mutius E: The asthma epidemic. N Englpared with airway devices such as the laryngeal mask airway. J Med 2006; 355:2226 –35 12. Bateman ED, Hurd SS, Barnes PJ, Bousquet J, Drazen JM,Basic science advances are needed in the understanding of FitzGerald M, Gibson P, Ohta K, O’Byrne P, Pedersen SE,the interaction between anesthetics, airway irritation, and Pizzichini E, Sullivan SD, Wenzel SE, Zar HJ: Global strategythe role of tachykinins and other C fiber neurotransmitters in for asthma management and prevention: GINA executive summary. Eur Respir J 2008; 31:143–78the control of airway tone. Moreover, the mechanisms by 13. Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW,which intravenous and inhaled anesthetics affect airway Casale TB, Chanez P, Enright PL, Gibson PG, de Jongste JC,nerves and directly modulate airway smooth muscle tone Kerstjens HA, Lazarus SC, Levy ML, O’Byrne PM, Partridgelikely involve modulation of plasma membrane ion channels, MR, Pavord ID, Sears MR, Sterk PJ, Stoloff SW, Szefler SJ, Sullivan SD, Thomas MD, Wenzel SE, Reddel HK: A newmembrane potential, and intracellular calcium sensitivity but perspective on concepts of asthma severity and control. Eurremain poorly understood. Respir J 2008; 32:545–54Anesthesiology 2011; 114:1200 –10 1209 Dewachter et al.
  11. 11. Bronchospasm during Anesthetic Induction14. Wenzel SE: Asthma: Defining of the persistent adult pheno- 28. Pizov R, Brown RH, Weiss YS, Baranov D, Hennes H, Baker S, types. Lancet 2006; 368:804 –13 Hirshman CA: Wheezing during induction of general anes-15. Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, thesia in patients with and without asthma. A randomized Togias A, Zuberbier T, Baena-Cagnani CE, Canonica GW, van blinded trial ANESTHESIOLOGY 1995; 82:1111– 6 Weel C, Agache I, Ait-Khaled N, Bachert C, Blaiss MS, Bonini 29. Brown RH: HRCT imaging of airway responsiveness: Effects S, Boulet LP, Bousquet PJ, Camargos P, Carlsen KH, Chen Y, of anesthetics. J Clin Monit Comput 2000; 16:443–55 Custovic A, Dahl R, Demoly P, Douagui H, Durham SR, van 30. Belelli D, Pistis M, Peters JA, Lambert JJ: General anaesthetic Wijk RG, Kalayci O, Kaliner MA, Kim YY, Kowalski ML, Kuna action at transmitter-gated inhibitory amino acid receptors. P, Le LT, Lemiere C, Li J, Lockey RF, Mavale-Manuel S, Trends Pharmacol Sci 1999; 20:496 –502 Meltzer EO, Mohammad Y, Mullol J, Naclerio R, O’Hehir RE, Ohta K, Ouedraogo S, Palkonen S, Papadopoulos N, Passal- 31. Hirshman CA, Edelstein G, Peetz S, Wayne R, Downes H: acqua G, Pawankar R, Popov TA, Rabe KF, Rosado-Pinto J, Mechanism of action of inhalational anesthesia on airways. Scadding GK, Simons FE, Toskala E, Valovirta E, van Cauwen- ANESTHESIOLOGY 1982; 56:107–11 berge P, Wang DY, Wickman M, Yawn BP, Yorgancioglu A, 32. Gallos G, Gleason NR, Virag L, Zhang Y, Mizuta K, Whitting- Yusuf OM, Zar H, Annesi-Maesano I, Bateman ED, Ben ton RA, Emala CW: Endogenous gamma-aminobutyric acid Kheder A, Boakye DA, Bouchard J, Burney P, Busse WW, modulates tonic guinea pig airway tone and propofol-in- Chan-Yeung M, Chavannes NH, Chuchalin A, Dolen WK, duced airway smooth muscle relaxation. ANESTHESIOLOGY Emuzyte R, Grouse L, Humbert M, Jackson C, Johnston SL, 2009; 110:748 –58 Keith PK, Kemp JP, Klossek JM, Larenas-Linnemann D, Lip- 33. Akao M, Hirasaki A, Jones KA, Wong GY, Bremerich DH, worth B, Malo JL, Marshall GD, Naspitz C, Nekam K, Nigge- Warner DO: Halothane reduces myofilament Ca2 sensitivity mann B, Nizankowska-Mogilnicka E, Okamoto Y, Orru MP, during muscarinic receptor stimulation of airway smooth Potter P, Price D, Stoloff SW, Vandenplas O, Viegi G, Wil- muscle. Am J Physiol 1996; 271:L719 –25 liams D: Allergic Rhinitis and its Impact on Asthma (ARIA) 34. Schaub B, von Mutius E: Obesity and asthma, what are the 2008 update (in collaboration with the World Health Orga- links? Curr Opin Allergy Clin Immunol 2005; 5:185–93 nization, GA(2)LEN and AllerGen). Allergy 2008; 63(Suppl 86):8 –160 35. Weiss ST, Shore S: Obesity and asthma: Directions for re- search. Am J Respir Crit Care Med 2004; 169:963– 816. Szczeklik A, Stevenson DD: Aspirin-induced asthma: Ad- vances in pathogenesis, diagnosis, and management. J Al- 36. Liccardi G, Salzillo A, De Blasio F, D’Amato G: Control of lergy Clin Immunol 2003; 111:913–21 asthma for reducing the risk of bronchospasm in asthmatics undergoing general anesthesia and/or intravascular adminis-17. Kumeta Y, Hattori A, Mimura M, Kishikawa K, Namiki A: A tration of radiographic contrast media. Curr Med Res Opin survey of perioperative bronchospasm in 105 patients with 2009; 25:1621–30 reactive airway disease. Masui 1995; 44:396 – 401 37. Smetana GW: Preoperative pulmonary evaluation. N Engl18. Schwilk B, Bothner U, Schraag S, Georgieff M: Perioperative J Med 1999; 340:937– 44 respiratory events in smokers and nonsmokers undergoing general anaesthesia. Acta Anaesthesiol Scand 1997; 41: 38. Sweitzer BJ, Smetana GW: Identification and evaluation of 348 –55 the patient with lung disease. Anesthesiol Clin 2009; 27:19. Westhorpe RN, Ludbrook GL, Helps SC: Crisis management 673– 86 during anaesthesia: Bronchospasm. Qual Saf Health Care 39. Ortega VE, Peters SP: Beta-2 adrenergic agonists: Focus on 2005; 14:e7 safety and benefits versus risks. Curr Opin Pharmacol 2010;20. Cheney FW, Posner KL, Lee LA, Caplan RA, Domino KB: 10:246 –53 Trends in anesthesia-related death and brain damage: A 40. Kramer JM: Balancing the benefits and risks of inhaled long- closed claims analysis. ANESTHESIOLOGY 2006; 105:1081– 6 acting agonists: The influence of values. N Engl J Med 2009;21. Cook TM, Bland L, Mihai R, Scott S: Litigation related to 360:1592–5 anaesthesia: An analysis of claims against the NHS in England 41. Barnes PJ: Mechanisms of action of glucocorticoids in 1995–2007. Anaesthesia 2009; 64:706 –18 asthma. Am J Respir Crit Care Med 1996; 154:S21– 6; discus-22. Auroy Y, Benhamou D, Pequignot F, Bovet M, Jougla E, ´ sion S26 –7 Lienhart A: Mortality related to anaesthesia in France: Anal- 42. Peters SP, Kunselman SJ, Icitovic N, Moore WC, Pascual R, ysis of deaths related to airway complications. Anaesthesia Ameredes BT, Boushey HA, Calhoun WJ, Castro M, Cherni- 2009; 64:366 –70 ack RM, Craig T, Denlinger L, Engle LL, DiMango EA, Fahy JV,23. Haxhiu MA, Kc P, Moore CT, Acquah SS, Wilson CG, Zaidi SI, Israel E, Jarjour N, Kazani SD, Kraft M, Lazarus SC, Lemanske Massari VJ, Ferguson DG: Brain stem excitatory and inhibi- RF Jr, Lugogo N, Martin RJ, Meyers DA, Ramsdell J, Sorkness tory signaling pathways regulating bronchoconstrictive re- CA, Sutherland ER, Szefler SJ, Wasserman SI, Walter MJ, sponses. J Appl Physiol 2005; 98:1961– 82 Wechsler ME, Chinchilli VM, Bleecker ER: National Heart,24. Jooste EH, Sharma A, Zhang Y, Emala CW: Rapacuronium Lung, and Blood Institute Asthma Clinical Research Network: augments acetylcholine-induced bronchoconstriction via Tiotropium bromide step-up therapy for adults with uncon- positive allosteric interactions at the M3 muscarinic recep- trolled asthma. N Engl J Med 2010; 363:1715–26 tor. ANESTHESIOLOGY 2005; 103:1195–203 43. Goff MJ, Arain SR, Ficke DJ, Uhrich TD, Ebert TJ: Absence of25. Kil HK, Rooke GA, Ryan-Dykes MA, Bishop MJ: Effect of bronchodilation during desflurane anesthesia: A comparison prophylactic bronchodilator treatment on lung resistance to sevoflurane and thiopental. ANESTHESIOLOGY 2000; 93: after tracheal intubation. ANESTHESIOLOGY 1994; 81:43– 8 404 – 826. Joos GF: The role of sensory neuropeptides in the pathogen- 44. Osuorji I, Williams C, Hessney J, Patel T, Hsi D: Acute stress esis of bronchial asthma. Clin Exp Allergy 1989; 19(Suppl cardiomyopathy following treatment of status asthmaticus. 1):9 –13 South Med J 2009; 102:301–327. Gleason NR, Gallos G, Zhang Y, Emala CW: Propofol prefer- 45. Green SM: Intravenous epinephrine in asthma? A word of entially relaxes neurokinin receptor-2-induced airway caution. Ann Emerg Med 2003; 41:712–3 smooth muscle contraction in guinea pig trachea. ANESTHESI- 46. Holley DA, Boots RJ: Management of acute severe and near- OLOGY 2010; 112:1335– 44 fatal asthma. Emerg Med Australas 2009; 21:259 – 68Anesthesiology 2011; 114:1200 –10 1210 Dewachter et al.