1. Pascale Dewachter, Claudie Mouton-Faivre, Charles W. Emala,Sadek Beloucif Anesthesiology 2011; 114:1200 10 DR. RISHABH MITTALMODERATOR DR. AVNISH BHARADWAJ

2. Case Report A 25-yr-old woman Body mass index: 54 kg/m2 ( morbidly obese) Noninsulin-dependent diabetes Scheduled for cochlear implant surgery. h/o 2 previous surgeries without incident during childhood. NO history of atopy or drug allergy Normal Chest auscultation before anaesthesia.

3. Case Report Anaesthetic coursePremedication Tab. Hydroxyzine (100 mg) the day before and 1 h before inductionInduction - Inj. sufentanil (20 g I.V) + Inj. propofol (350 mg I.V) Tracheal Intubation (Cormack and Lehane grade I) - Inj. succinylcholine (130 mg I.V). Chest auscultation -complete absence of bilateral breath sounds. End-tidal carbon dioxide (ETCO2) - Low. initially

4. What had happened?? SUSPECTED -Esophageal intubation ?? Patient immediately extubated Mask ventilation attempted - difficult to perform Dramatically decreased lung compliance ETCO2 - marked prolonged expiratory upstroke of the capnogram Bronchospasm !!!!!!!!

5. What was DONE?? WITHIN FIVE MINUTES SpO2 55%, Arterial hypotension ( From 130/75 to 50/20 mmHg), Moderate tachycardia (100 beats/min) Titrated epinephrine (two I.V boluses of 100 g each) , Ringer lactate- 1000 ml Blood pressure, 110/50 mmHg; heart rate, 110 beats/min), Ventilation became easier to perform Audible wheezing over both lung fields. A localized (face and upper thorax) erythema - Hydrocortisone(200 mg) I.VBlood sample 40 and 90 min after the clinical reaction- to measure serum tryptase concentrations

6. And then.. Surgery was postponed Patient was transferred to the intensive care unit. Inhaled 2-agonist (salbutamol) I.V corticoids (hydrocortisone, cumulative dose: 800 mg over24 h) Respiratory symptoms resolved within 2 h h/o wheezing induced by cold and exercise was elicited No additional supportive vasopressor therapy was required Patient discharged home the following day Allergologic assessment - after 6 wk

7. Bronchospasm?? Is defined as constriction of bronchi and bronchioles Clinical feature of exacerbated underlying airway hyper- reactivity symptoms include difficulty in breathing, wheezing, coughing, and dyspnea. Chest auscultation wheezing decreased or absent breath sounds - critically low airflow.

8. Peri-operative bronchospasm.. Usually arises during induction of anesthesia May be detected at any stage of the anaesthetic course. Bronchoconstriction due to - Immediate hypersensitivity reaction EVOKING ALLERGY I. IgE-mediated anaphylaxis II. Anaphylactoid reaction Non immune Mechanism Non-allergic mechanism triggered by I. Mechanical factors ( intubation-induced bronchospasm) II. Pharmacologic factors (via histamine-releasing drugs such as atracurium or mivacurium )

9. D/D of Intra-operative Bronchospasm Esophageal intubation Inadequate anaesthesia Mucous plugging of the airway Kinked or obstructed tube/circuit, Pulmonary aspiration. Unilateral wheezing suggests endobronchial intubation or an obstructed tube by a foreign body (such as a tooth). If the clinical symptoms fail to resolve despite appropriate therapy, pulmonary edema or pneumothorax should be considered.

10. Periop. Immediate Hypersenstivity Reaction Clinical entity evoking allergy that varies in severity Occurs within 60 min after the injection/introduction of the culprit agent Diagnosis is linked to a triad including - 1. Clinical features ( Graded acc. to Ring and Messmer clinical severity scale) 2. Blood tests (Tryptase level measurements, serum-specific IgEs) 3. Postoperative skin tests with the suspected drugs or agents

11. Ring and Messmer clinical severity scale 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 bronchospasm cutaneous-mucous signs gastrointestinal disturbances; Grade IV: Cardiac arrest

12. Etiology in the Current Case Clinical diagnosis initially suggested drug-induced anaphylactic reaction (allergic bronchospasm) Sudden occurrence of bronchospasm after induction Cardiovascular disturbances Cutaneous signs Succinylcholine-induced anaphylaxis was suggested as the most likely etiology at first sight. Neuromuscular blocking agents are the most frequent agents involved in perioperative anaphylaxis in adults

13. Etiology in the Current Case How can we differentiate between allergic and non- allergic bronchospasm clinically?? Clinical variables predicting IgE mediated anaphylaxis Presence of any cutaneous symptoms ( 7times) Shock (cardiovascular collapse) HALLMARK (27 t1mes) Episodes of desaturation (22 times) Prolonged duration of clinical features (longer than 60 min) Cardiovascular collapse -usually the inaugural clinical event , occur within minutes after the drug challenge May occur either before or after instrumentation of the airway

14. Etiology in the Current Case Non-allergic bronchospasm Immediately follows nonspecific stimuli (irritation by ETT, suction catheter) Usually not associated with cardiovascular symptoms but.. PEEP with severe bronchospasm may lead to a decrease in venous return & hence cardiac output. Hypoxia and respiratory failure from inadequate ventilation may lead to cardiovascular collapse (occurs late after bronchospasm) Cutaneous signs may be observed

15. Etiology in the Current CaseIn the current case Skin testing remained negative in response to propofol, sufentanil, succinylcholine, and latex solutions. Tryptase level were unchanged (N less than 13.5 g/l.) - specific for mast cell activation Serum-specific IgEs against succinylcholine and latex were not detectable. Basophil activation test- Succinylcholine induced neither CD63 nor CD203c up-regulation. Succinylcholine-induced anaphylaxis was ruled out

16. Etiology in the Current Case Bronchospasm triggered by endotracheal tube insertion and followed by cardiovascular collapse (hypoxemia) suggests non-allergic bronchospasm Erythema may also be observed during non-allergic bronchospasm. Morbid obesity of the patient -precipitating factor of rapid arterial desaturation Uncontrolled Asthma -main trigger of this non-allergic bronchospasm (h/o wheezing induced by cold and exercise elicited from patient in post-op period)

17. What is ASTHMA??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. (2008)

18. ASTHMA Two main phenotypes:- Allergic Non-allergicOverlap may occur within these groups Allergic Rhinitis and Allergic Asthma Belong to the Same Airway Disease -More than 80% of asthmatic individuals have rhinitis, and 1040% of patients with rhinitis have asthma

19. Allergic Asthma Onset occurs primarily in early childhood Results from immunologic reactions, mostly initiated by IgE antibodies Atopy - (Genetic predisposition for the development of an IgE- mediated response to common aeroallergens) - strongest identifiable predisposing factor Triggers- Environmental factors - tobacco smoke, air pollutants, and exposure to allergens Obesity, diet, and hygiene hypothesis ATOPY + TRIGGERS ALLERGIC ASTHMA

20. Non-allergic Asthma: Aspirin-induced Asthma Widely under diagnosed condition Not seen in childhood Inhibition of cyclooxygenase enzymes by aspirin-like drugs in the airway of sensitive patients Characterized by eosinophilic rhinosinusitis, nasal polyposis, senstivity to aspirin or NSAIDs and asthma Rhinorrhea, nasal congestion, and anosmia are the first clinical features Asthma and sensitivity to aspirin appear approximately 15 yr after the onset of rhinitis

21. Perioperative Bronchospasm & AsthmaWesthorpe RN, Ludbrook GL, Helps SC: Crisis management during anaesthesia: Bronchospasm. Qual Saf Health Care 2005; 14:e7In a study conducted by Westhorpe RN et al (103 cases)PERIOPERATIVE BRONCHOSPASM Allergic (21%) / Non-allergic mechanism(79%) Of Non-allergic cases, 44% during induction, 36% during maintenance phase, and 20% during emergence/recovery stage. Major causes during - Induction - airway irritation (64%), tube misplacement (17%), aspiration (11%), and other pulmonary edema or unknown causes (8%). Maintenance -allergy (34%), endotracheal tube malposition (23%), airway irritation (11%), aspiration with a laryngeal mask airway(9%)

22. Perioperative Bronchospasm & Asthma Bronchospasm induced by airway irritability occurred more frequently in patients who had one or more predisposing factors such as asthma, heavy smoking, or bronchitis. Previous history of asthma was present in 50% cases of Non-allergic Bronchospasm 60% patients with allergic bronchospasm Uncontrolled asthma/chronic obstructive pulmonary disease is frequently involved with both allergic and non-allergic bronchospasm, regardless of the stage of anesthesia (induction or maintenance)

23. Mechanisms of Reflex-induced Bronchoconstriction Irritation of the upper airway by a foreign body Afferent sensory pathwaysStimulatory - Glutamate++ Nucleus of solitary Tract Inhibitory- aminobutyric acid - -Glutamate++ Airway-related Vagal Pre- ganglionic Neurons Airways via Vagus nerve Acetylcholine release ++ Bronchoconstriction (M3 muscarinic receptor)

24. Reflex-induced Bronchoconstriction Non-adrenergic non-cholinergic nerves (releasing tachykinins, vasoactive intestinal peptide, and calcitonin gene-related peptide) may participate in this reflex arc and/or locally release the pro- contractile neurotransmitters via activation of inter-neurons in the airway. Since Acetylcholine acting on M3 muscarinic receptors on airway smooth muscle is a key component in mechanism, use of antimuscarinic - inhaled medications (e.g., ipratropium or tiotropium) should be advantageous to prevent /treat it.

25. Reflex-induced Bronchoconstriction Propofol and volatile inhalational anaesthetics (except desflurane) are clinically effective Have activity at inhibitory GABA-A chloride channels Have direct bronchodilatory effects at the level of airway smooth muscle (via GABA-A channels/ modulating calcium sensitivity of the contractile proteins) Propofol preferentially relaxes tachykinin- induced airway constriction Deepening anesthesia Prevents /relieves reflex-induced bronchoconstriction Modulation of GABA input to the airway-related vagal preganglionic neurons from the nTS/ higher centers

26. BUT. Despite these protective effects of intravenous propofol and the adequate induction dose used in the current case, reflex-induced bronchoconstriction developed in this patient who had previously unrecognized and untreated asthma.

27. Obesity and Asthma: Is There Any Relationship? Obesity- body mass index of at least 30 kg/m2 Both are systemic inflammatory states Chromosomal regions with loci common to obesity and asthma phenotypes have been identified Obesity FRC & TV contractile responses of airway smooth muscle airway reactivity

28. Obesity and Asthma: Is There Any Relationship? Gastroesophageal reflux resulting from obesity may potentially trigger a latent asthmatic condition Hormonal influences- hormone leptin produced by adipocytes has effects on immune cell function and inflammation Recent changes in lifestyle and diet are associated with both Asthma remains under diagnosed in obese patients - respiratory symptoms are frequently attributed to being overweight (current case) Sleep-disordered breathing is more prevalent in asthmatic as well as obese individuals

29. Prevention of Perioperative Bronchospasm Acc. To Global Initiative for Asthma guidelines - Perioperative and postoperative complications rely on Severity of asthma at the time of surgery Type of surgery (thoracic /upper abdominal surg risk) Modalities of anesthesia (GA with intubation risk) Uncontrolled asthma is considered to be the main risk factor for bronchoconstriction during surgery.

30. Prevention of Perioperative BronchospasmHISTORY Poorly controlled Asthma may be assessed through Degree of asthma control (inc. Use of medications, recent exacerbations of symptoms, hospital visit within the last months) Potential risks or complication factors (recent respiratory tract inf., previous bronchospasm / pulmonary complications during/after previous surg, long-term use of a systemic corticosteroids, assso. gastroesophageal reflux or smoking). Abstinence from smoking before surgery reduces perioperative pulmonary complications

31. Prevention of Perioperative BronchospasmPreoperative Clinical and Physical Examination Acc. To Smetana et al perioperative pulmonary complications occur if preoperative examination reveals - Decreased breath sounds Dullness to percussion Wheezing Rhonchi Prolonged expiratory phase In the presence of active bronchospasm, elective surgery should be postponedSmetana GW: Preoperative pulmonary evaluation. N Engl J Med 1999; 340:937 44

32. Prevention of Perioperative BronchospasmMeasurement of lung function (PFT) FEV1 /PEFR -better indicators of the severity of asthma exacerbation than clinical symptoms. FEV1/ FVC (normal > 75%) - sensitive measure of severity and control Reversibility with the use of a bronchodilator defined as increase in FEV1 of at least 12% or 200 ml. Before surgery PEF or FEV1 >> 80% of the predicted or personal best is recommended. If PEF or FEV1 is