[Asthma How 11 1 CHEST Management of Life-Threatening Asthma (@ assis Severe Asthma Series Oriando Gamer, MD; James Scott Ramey, MD; and Nicola A. Hanania, MD, FCCP ‘Asthma exacerbations can be lfe-threetening, with 25,000 to 50,000 such patients per year requiring admission to an ICU in the United States. Appropriate triage of life-threatening ‘asthma Is dependent on both static assessment of airway function and dynamic assessment ‘of response to therapy. Treatment strategies focus on achieving effective bronchodilation with Inhaled fa-agonists, muscarinic antagonists, and magnesium sulphate while reducing Inflam- ‘mation with systemic corticosteroids. Correction of hypoxemia and hypercapnia, @ key in ‘managing life-threatening asthma, occasionally requires the incorporation of noninvasive me chanical ventilation to decrease the work of breathing. Endotracheal intubation and mechanical ventilation should not be delayed if clinical improvement Is not achieved with conservative therapies. Honever, mechanical ventilation in these patients often requires controlled hypor ventilation, adequate sedation, and occasional use of muscle relaxation to avoid dynamic hy- perinflation, which can result in barotrauma ar volutrauma. Sedation with Ketamine or propofol is preferred because of their potential bronchodiiation properties. In this review, we autine strategies forthe assessment and management of patients with acute life-threatening asthma focusing on these requiring admission to the ICU, (CHEST 2022; 162(4):747-756 ‘key WoRDS: critical care medicine life-threatening asthma; mechanical ventilation; respiratory failure; sedation Introduction ‘mechanical ventilation. In one study, of Patients with asthma often experience severe ‘exacerbation of the disease that, on occasion, ‘may be life-threatening Although the provalence of asthma generally has increased in most countries, the incidence of life. threatening exacerbations has decreased ‘because of the improvement in management strategies, therapies, and health-care access.” tis estimated that of 2 millon patients with asthma exacerbations seeking treatment at the ED in the United States every year, approximately 25,000 to 50,000 patients will require ICU admission, with some requiring 33,000 patients with acute asthma exacerbation requiring hospital care, 10.1% required admission to the ICU and 2.1% required intubation and invasive ‘mechanical ventilation (IMV}.’ Therefore, it is imperative for clinicians working in an ICU tobe familiar with the proper assessment and ‘management strategies of life-threatening asthma exacerbation (LAB), Case Presentation A AL-year-old man with history of asthma was seen in the ED reporting shortness of Poa membrane oxygenation: HENC Ty vase mechaniol sentation, UTAE. = We-thresening suthms eacertation: NIV muscle blockade Peak exprtory flow: Fpaw dynamic hperiniaton: ECMO = exaso gow asa annus oninasive vention: NMI = near tbe end-expiratory prsure PEE thovay presre SA~ sai oe cng Be agonists SpO, = oygen strain ‘arruuarions: From the Section of Plone Ceeal Care and ‘Seep Medicine (0. Garner ana N A Hania} and Ue Depart of Modine 18: Raney) yor Calege of Metin, Howton, TX. CORRESPONDENCE TO: Orlando Garner, MD: emaik 03100 Copyright © 2022 American Calley of Chest Pins, Pushed by bev Ie ll ghts reserved Ot itps/diony/ 10.101. ches. 2022.02025 7breath, productive cough, and wheezing that began 3 days previously. He did not report fever, sick contacts, chest pain, nausea, vomiting, oF refiux, but had nasal ‘congestion and postnasal drip of 1 year's duration, He disclosed that he recently was discharged from the hospital ater experiencing another asthma exacerbation, but had not filed the preseription given to him on discharge for controller medication and had been using “only his rescue medication multiple times during the day and night. He has five dags at home and has a 10-pack- ‘year history of smoking, On examination, temperature ‘was 36°C heart rate was 116 beats/min, respiratory rate ‘was 28 breaths/min, and BP was 164/79 mm Hg, with an ‘oxygen saturation (SpO,) of 90% on room ait. He vas sitting upright, using accessory muscles, and could not speak in complete sentences, Cardiac examination revealed tachycardia without any extra heart sounds. Diffase wheeves were heard throughout both lung feds. In the ED, he was started on albuterol nebulization every 20 min along with oxygen 3 1 by nasal cannula, improving SpO, to 93%. However, the work of breathing did not improve, and abslominal paradox was observed at bedside. Chest radiography showed hyperinflation, Dut no infiltrates, and venous blood gas revealed a pH of 7.28 and Pco; of 54 mm Hig. The patient received 125 mg of methylprednisolone intravenously and an infusion of 2g of magnesium sulfate and was started on high-flow nasal canna How We Do It Triaging Appropriate disposition is vital in the management of acute asthina to avoid complications and to prevent death, Danker etal" proposed a simplified severity score for asthma evaluation inthe ED. This score (Fable 1)" is ‘Taste 1] Simplified Severity Score for Acute Asthma’ based on six parameters obtained by clinical evaluation and clasiies patients according to mild, moderate, and severe exacerbations, Severe and moderate exacerbation sgroups have an OR for hospitalization of 12.2 (95% CI, 7.5-19.9) and 5.6 (95% Cl, 35-8), respectively, when compared with the mild exacerbation group. A simplified severity score may aid in disposition of patients in the ED and in the decision for ICU. admission, Stati assessments (SAs) and dynamic assessments of acute asthma exacerbation in the ED also can help to Urlage patients. SA looks at severity at presentation, which in turn determines the aggressiveness of initial ‘weatment. $A includes obtaining bistory of treatment adherence, severity of current exacerbation compared ‘with previous episodes, and prior hospitalization or need for mechanical ventilation, Physical examination also can help to determine severity of illness. Tripoding and use of accessory muscles correlate with increased severity. Similarly, the absence of breath sounds (silent Jungs) and presence of abdominal paradox breathing are re-flag features of an underlying life-threatening asthma episode. Objective SAs include the measurement of peak expiratory flow (PEF), FEV, or both, A severe exacerbation usually is defined as a PEF or FEV, of less than 50% to 60% of predicted normal values, Dynamic assessment is more helpful because it gauges response to treatment, A lack of improvement in expiratory flow rates after initial bronchodilator therapy with continuous of worsening symptoms suggests the reed for hospitalization.” Ventilation and perfusion ‘mismatch is very common in acute asthma, and significant hypoxemia and hypercapnia may occur luring an acute severe episode. However, depending on ‘oxygen saturation alone sometimes may be misleading, See Soe Sine Soto Wid teat Tse rat, beatin Te cerry Tine wheezng Absent Present resent rales Absent Present Present Prolonged exp Absent Present resent oxygen satraton, % 95-100 90-56 «eo Use accessory muscles Aosent Present resent Minima no. of erameters | Any ofthe above | Any 3ofthe above or the use | Any 3 ofthe above or oxygen requred to gusty for ‘of ecessory muscles only” | ~setreton of 85% only ‘otegores 748 How 1Doit [ 26244 enest ocrosen 2022 ]and therefore blood gas examination or end-tidal ‘apnography often are valuable tools for complete assessment, ICU admission should be considered in patients with hypoxemia (SpO; < 92%) despite the use ‘of supplemental oxygen, worsening hypercarbia, ‘encephalopathy, presence of arrhythmia, or evidence of barotrauma (pneumothorax or peumomediastinum) or for those who require oxygen by high-flow nasal cannula (ENC), noninvasive ventilation (NIV), oF IMV Pharmacologic Management of Acute Asthma ‘The main therapeutic goals for acute asthma ae reversal of bronchospasm and correction of hypoxemia, In ation, implementing plans to prevent recurrence i ‘rial, The comerstone, inal, conventional pharmcologic mamegeméat of acute sthros inctades the administration of repeated doses of inhaled short acting Be-agonists (SABA®) inhaled short-acting anticholinergics (short-acting muscarinic antagonists). systemic corticosteroids, and on occasion, IV ragsinm slate Inhaled SABAs: SABAs are the first-line treatment for acute asthma, Continuous nebulization of albuterol is a safe approach, but intermittent dosing also is reasonable and is implemented more commonly (Table 2). Use of metered-dose inhalers with spacers allows for targeted alluterol dosing, but offers no signiticant advantage aver nebulization.”* Also a high-dose strategy (7.5 mg) offers ro benefit over a low-dose (2.5 mg) of albuterol.’ IV fr agonists should be reserved for when inhaled therapy is not feasible." By-Agoniss with higher intrinsic eficay (ll agonists), such as formoterol and isoproterenol, may offer a theoretical advantage over a partial agonist such as albuterol, expecially when the latter does not yield a significant response. For example, the full agonist isoproterenol demonstrated superiority to albuterol in improvement of lung function and symptoms in asthma ‘exacerbations. However the potential for systemic adverse effects by activating receptors on nontarget sites such as the heart is higher. Inhaled Short-Acting Muscarinic Antagonists: Ipratropium bromide relaxes bronchial smooth muscle by antagonizing the muscarinic M3 receptor on smooth muscle ofthe airway, alleviating airway obstruction. Compared with SABAs, it has a slower onset of action (60-90 min) coupled with an average potency (159% increase in PEF) and unsustained benefits after ED admission. When used, ipratropium bromide should be chestouraLors administered in combination with SABAS, and it seems that its benefit is limited to patients with severe disease." Systeme Corticosteroids: Systemic corticosteroids improve outcomes in patents with acute asthma and reduce the likelihood of repeat exacerbation, They should be administered as soon as possible, because clinical effets may take 6 0 12h to take effect Although no sgeilicant difference inefficacy exits between oral and IV corticosteroids, the degree of respiratory distress may dictate the route of administration, ® We recommend stating with 1V rmethyipredisolone in those with severe respiratory distress who aze being admitted to the hospital or ICU. ‘The potential role of inhaled corticosteroids in ‘managing acute asthma has not been evaluated flyin large als although some studies in children and adults suggest a benefit.” ‘Magnesium Sulphate: Magnesium sulphate acts as a bronchodilator by inhibiting calcium channels and blocking parasympathetic tone.'" The role of IV ‘magnesium in the treatment of acute asthma has been studied as an adjunct therapy to SABAS, ipratropium bromide, and corticosteroids. Evidence has shown that this intervention reduced hospital admissions in severe asthma and improved pulmonary function, but it has not been found to reduce mortality or need for NIV.” The use of nebulized magnesium sulphate is much less clear, and studies have not shown consistent benefit!" Controlled Oxygen Therapy: Acute asthma is associated with significant VQ mismatch with perfusion of nonventilated areas causing hypercarbia and hypoxemia." If concomitant hypoxemia oceurs (Pao; < 55 mm Hg or SpO2 < 9%), oxygen therapy should be initiated with a goal SpO, of > 92%, Hyperoxia may be harmful in some patients and should be avoided whenever possible” A randomized controlled trial found that patients who received 289% oxygen, compared with 100% oxygen, showed a fll in Paco, and those in the latter group showed an increase.” Therefore, conservative SpOs targets should be pursued in patients with acute severe asthma and those with impending respiratory failure. HIPNC: Although HENC is usefal in patients with respiratory failure such as acute lung injury and ARDS, its role in acute severe asthma has not been well established. A study of 36 patients assigned to either HENC or conventional oxygen therapy did not demonstrate any difference in clinical response, 749‘Taste 2] Pharmacotherapy in Asthma Exacerbation Paton Dose Gamer Inhaled bronchodilators Abuterol nebulization 2.5-5 mo every 20 min for 3 doses, then 2.5-10 mg every 1-4 has needed of 410-15 mg/h continuously oI (90 ua/out) 48 puffs every 20 min up to 4h, then every 1-4 nas needed {Isoproterenol nebulization 7.5 math for 2m Ipratropium bromide 10.5 mg every 20 min for 3 doses, then as. nebulization needa Mor ' putts every 20 min as needed upto 3h ‘ystemic bronchodilators Epinephrine 14 1:1,000 (1 mart) (0.3-0.5 mg IM every 20 min up to 3 doses Subeutaneous 1:1,000, 10.3-0.5 mg subcutaneously every 20 min up (mgmt) 103 doses Intravenous 0.4 na/kg/min Terbutaine Subostaneous (0,25 mg subcutaneously every 20 min for ‘3s doses Intravenous Bolus 4-10 ua/kg folowes by continuous Infusion of 0.2-0.4pa/kg/min Albuterol . Intravenous 10-15 pa/kg (maximum, 250g) over 5-10 min, which can be repeated every § min Aminophyline Intravenous {6 maka over 30 min followed by an infusion 2F0.5 mark conseostereite ethylprecnisolone 40-60 mg IV every 6h for 24 h, taper to 140-60 every £2 hI improv Prednisone -40.mg po dally for 54 ther medications Magnesium sulfate 1.2g1V over 20 min ‘Sedatives and muscle relaxants Ketamine Subanesthetic dosing Infusion | 0.1-0.5 mg/h Dissociative dosing infusion | 1-4 ma/h Dexmedetomidine Infusion 0.2-0.7 nalkayn Propofol a Infusion 5-50 pa/ko/min Gsatracurium we 1V bolus followed by infusion | Loading 0.4-0.2 mg/kg followed by infusion of 1-3 ug/kg/min ‘No longer available Inthe United ‘States ‘Thrate by 0.1-0.2 na/ka/min based ‘on response or taxicty ‘Not available n the United States ‘Not recommended by current guidelines ‘Serum levels shouldbe checked and kept between 8 and 12 pa/m. May cause laryngospasm May cause myocardial depression ead one hale 780 How Dott [ 26244 enest ocrosen 2022 ]although a signal of improved heart and respiratory rate was found in the HENC group.” HENC can be used in acute severe asthma, but it should not delay the use of NIV or endotracheal intubation. Case Presentation: Update ‘The patient was admitted to the ICU; however, respiratory distess worsened despite treatment. He became unable to speak and continued to assume a tripod posture, and subcostal retractions became notable, He became hemodynamically unstable, with minimal tachypneic and lung sounds. The patient ‘progressed to LTAE, prompting a move to the ICU, and, warranted consideration for other avenues of treatment and respiratory support. Pharmacologic Management of LTAE Systemic Bz-Agonists: When inhaled SABA treatment is not possible, 1V albuterol is recommended by some national guidelines, although itis not available in the United States." ” Epinephrine has bronchodilting effects and can be used with various presentations (Table 2. Systemic terbutaline is another Ba-agonist that «an be used for asthma refractory to inhaled therapeutics. hough strong evidence of superiority of its use is lacking, it ean be useful in patients who are not responding to conventional therapy. Caution is advised in patients with tachyarchythmias and hypokalemia.” Side effects include those commonly seen with inhaled albuterol, including hypokalemia, hyperlctatemia, hyperglycemia, tachycardia, and tremors.” Methylxanthines: Aminophylline is a methylxanthine that traditionally has been used as an infusion in acute asthma, It is a nonselective phosphodiesterase inhibitor. However, aminophylline isan inferior bronchodilator to SABA monotherapy. Furthermore, aminophylline is associated with an inereased risk of nausea, vomiting, and tachyarshythmias, Because of the safety profile of minophyiline, its use is no longer recommended in the treatment of acute asthma.” Heliox (Helium Plus Oxygen) Normal airflow in the medium and small airways is laminar; during a life-threatening asthma episode, airflow in these airways often becomes turbulent, increasing the work of breathing, Helium has a lower density and higher viscosity than regula air, and thus ‘can improve airflow through narrow airways. Helix isa ‘combination of helium and oxygen that reduces turbulent flow and promotes laminar flow. However, Fro, requirements need to be < 30% for its proper use chestouraLors Heliox has two preparations, 0:30 and 80:20, which can be delivered via face mask, nebulizer, or nonrebreather ‘mask or through IMV.” A meta-analysis found that hhliox was associated with improvement in PEP, especially in severe (PEF > 50% predicted) and very severe (PEF < 50% predicted) exacerbations.”” Heliox can be used in patients with severe bronchospasm who do not respond to conventional therapies to facilitate ‘medication delivery, and it ha been reported to decrease dynamic hyperinflation (DIN), reducing the work of breathing and hypercarbia. Its effets in reducing intubation remain unknown. We favor using heliox over not using it. If intended effets are not seen within 15 rin, the therapy should be abandoned. Biologics Interest has been expressed in the use of biologics to reduce eosinophils in those with asthma, Benralizumab isan IL-S receptor antibody that has been able to produce eosinopenia after a single dose. Nowak etal!” demonstrated that single-dose benalizumab coupled with steroids reduces the rate and severity of exacerbations in those seeking treatment at the ED and suggested possible eficacy in patients with asthma exacerbations with contraindications to steroids. However, the usefulness of other biologics in treating acute asthma has not been evaluated, and none of them is approved for treatment of acute exacerbations. Ventilation in LTAE NIV’ Few studies have examined the effect of NIV (either biphasic positive pressure ventilation or CPAP) fn patients with LITAE. A Cochrane review concluded thatthe use of NIV with standard of care may be beneficial. Although no clear benefit in mortality or rate of intubation was found statistically significant Improvements occurred in respiratory rate, PEF, FEV, number of hospital admissions, and length of ICU and hospital stays." CPAP at 10 em H,0 can be used as a rescue therapy from intubation, although we favor the use of biphasic positive pressure ventilation.”* Biphasic positive pressure ventilation allows use of expiratory positive airway pressure to match autopositive end-expiratory pressure (PEEP) and inspiratory positive airway pressure to create a driving pressure to support the work of breathing, We recommend starting at an expiratory positive airway pressure of 5 cm H;0 and an inspiratory. positive airway pressure of 10 cm HO and titrating Fics for a goal SpO; of approximately 92%. Inspiratory 751postive airway pressure should be titrated for improvement in the work of breathing. Intubation is recommended if no improvement in the work of breathing, PEP, FEV, or Poo, occurs within 30 to {60 min of initiation IMV‘ Endotracheal intubation remains a rare event in patients with asthma, due in part to the improved ‘therapeutics and reversible nature ofthe disease but some patients will require IM. This s especially true in patients with refractory bronchospasm. Ideally most patients can be rescued from intubation, but those who present with frank respiratory distress, encephalopathy ‘or are hemodynamically unstable should be intubated. Aieway management of patients with LTAE is crucial because they usually have poor reserve, bag-mask ventilation can further worsen DHE, acidosis ean precipitate cardiac arrest, and hemodynamic instability ‘ay arise from insensible losses, Patients with LAE should always be considered as difficult airways due to potential complications that may arise peri-intubation, ‘A lange endotracheal tube (> 8 mm) is favored to relieve the airway resistance generated through IMV.™ Delayed ‘sequence intubation isan alternative to rapid sequence intubation that can be beneficial in LTAE, Delayed sequence intubation intends to separate the induction agent from the paralytic to resuscitate, preoxygenate and denitrogenate beter. Per-intubation resuscitation ean prevent hemodynamic instability in patients who might have become hypovolemic from insensible losses.” The shock index isa simple bedside caeulation (heart rate systolic BP) that can help to identify occult shock and is predictive of peri-intubation cardiac arrest. If a patient hhasa shock index of > 1, pre-emptive resuscitation with fluids or vasopressors is needed.” Ketamine should be used as an induction agent because it does not cause hemodynamic instability.” As soon as the SpO: goal i achieved, paralysis with rocuronium is favored, Rocuronium wil allow patients to be passive while receiving IMV alter intubation, facilitating ventilator management. Bag-mask ventilation should be avoided because it ean worsen DHL or cause barotrauma. Barotrauma occurs as a result of high pressures in distal airways, Pheumomediastinum or pneumothorax must ‘be suspected in patients with tracheal deviation, crepitus, ‘or sudden loss of breath sounds, Imaging studies are required to make the diagnosis. Portable chest radiographs may be used, but may not be readily available. Point-ofcare ultrasound can be useful, but hyperinflated lungs may be confounded by 752 How Dott pneumothoraces, Detection of pneumothorax on point cof-care ultrasound depends on the lack of movement of the parietal pleural on the visceral pleura, which is seen in patients with asthma exacerbation." Invasive mechanical ventilation goals in LTAE are to improve delivery of inhaled bronchodilators, to improve work of breathing, and to reduce DHI while preventing volutrauma and barotrauma, IMV can be detrimental in LTAE because it adds positive pressure to an already high airway pressure, exacerbating DHI further. Excessive DHI affects preload through high intrathoracic pressure, resulting in hemodynamic instability. forts must be made to relieve airway pressure and to decompress DHI with the ventilator settings. ‘Mechanical ventilation can be achieved with either assisted and controlled volume-cycled ventilation or with assisted and controlled pressure-cycled ventilation. ‘The focus of intial ventilator settings should be to reduce DHI and to prevent lung injury. This is achievable by manipulating the minute ventilation, inspiratory to expiratory ratio, and peak airway pressure (Ppave. Initially a low respiratory rate (8-10 breaths! min) should be set to allow a prolonged expiration (Fig.1). Monitoring HI response to low minute ventilation can be seen in flow-time scalar, The expiratory portion of this scalar should come back to baseline before a new breath is initiated, suggesting resolution of DHIL If breath stacking continues (ie, flow- time curve does not return to 0 before a new breath is started), decreasing the inspiratory time will allow for & faster breath to be delivered and for more time to be spent in expiration atthe expense of increased Ppaw. Iealy, the inspiratory to expiratory ratio should be set at 12, but in LTAE, a ratio of 13 or 1 is acceptable. IF breath stacking persists, disconnection from the ventilator cizcut while gently compressing the chest for +30 to 60 s can be performed. Gentle chest compressions at end expiration during IMV has been reported as a ‘maneuver to improve DHL Deep sedation, ot neuromuscular blockade (NMB), may be needed." ‘The tidal volume should be set approximately 6 to 8 mL! kg of ideal body’ weight. Careful atention should be paid to plateau pressure, with a goal of < 30 em HO while adjusting tidal volume or respiratory rate to avoid lung injury. Ventilation may be limited because of high Ppaw and plateau pressure, but usually hypercarbia is well (olerated up to Pacos of 90 to 100 mm Hg, Permissive hypercarbia should be allowed to a pH of > 7.20in those [ 26244 enest ocrosen 2022 ]War iocman conser Bap semteo Systane Broveredao “Ted H elon necropsy fs Dreamin pHc720, Peo, 90 rene al Stings ‘AGF, 00%, F810 eatin PEEP Sbem20, TV6ig or Conse Bronchoscopy NAG #ateaase Gee Arete ECMOECoOee | | “weummestaton, Figure Flowchart sowing « managoret of if estening ats escerbation lori, AC ais contro EOCO-R ‘xracoporal mien oxygenation, EDAD = espatory postive erway presane [BW ~ Mel body weight ‘carbon dade roa ECHO IMU" mechanical eatin: MgSO, = mas spate: No panto er apr pra: oreo §pOs ~ exygen satan patients without any contraindication (eg, myocardial ‘depression or intracranial pathologic features). uttnsc PEEP should beset at ow level in intubated Patients (< 5 em H,0), Spontaneously breathing patients ‘may benefit fom matching the auto-PEEP withthe extrinsic PEEP, This improves the work of breathing by decreasing the chestouraLors Keo Pt 0 or Woes dren hypetaion a Seen Sesreees “Mechanical Chest Compression ctrcoporea Inaderats NAC Neacelcine NMB = neromuca Blockade PEEP = say rales SABA = sor acting Begs SAM. Ipiatry tne, TY tal volume sor ating macaroni CS = oemie pressure gradient nec to overcome the auto-PEEP. ‘Measuring aito-PEEP should occur at last every 6h. io» intially should be set at 100%, but then rapidly titrated down for a goal SpO; of > 92%. hypoxia persists, a workup for alternative causes, including pulmonary shunting, should ensue," 753Nonventilatory Strategies for LTAE Sedation: Patients with LTAE exhibit a degree of breathlessness and feeling of imminent death that are dotrimental to NIV use or inhaled medication delivery. Light sedation can be used to help patients tolerate NIV and to deliver inhaled bronchodilators effectively. Deep sedation, with oF without neuromuscular blockade, may. bbe warranted in those requiring IMV. Use of sedatives should warrant an admission to the ICU because patients will require frequent monitoring Im a nonintubated patient, intermittent dosing of sho acting opioids can decrease breathlessness and can depress respiratory drive. Boluses of fentanyl can be used because it has a rapid onset of action and a short half-life, IF» favorable response occurs, doses can he repeated every 30 min as needed. Morphine should be avoided because it can cause histamine release. Dexmedetomidine is an ay-agonist that can be used if more sedation is needed. It does not suppress the respiratory drive and causes appropriate anxiolysis, Effects will be seen within 5 to 15 min, which may be too long in some patients, Ketamine is an N-methylD-aspartate receptor antagonist that can be used at subanesthetic dosing of at dissociative dosing, Ketamine works within seconds, vill, not cause respiratory depression, and can have a bbronchodilation effec. Infusions are started at ssubanesthetie dosing and titrated slowly up to effect. Side effects include bronchorrhes, salorrhea, and laryngospasm, Benzodiazepines should be avoided because they ate associated with worse outcomes, As soon as ketamine or dexmedetomidine infusions are started, equipment and induction medications for intubation should be avaiable readily at bedside, Propofol is a good first choice for patients receiving IMV. It allows for deeper sedation and synchronization ‘with the ventilator and has bronchodilatory propertis. Using ketamine concomitantly also can potentiate the bronchdilation and can reduce propofol and opioid requirements, possibly decreasing the number of days of IW. Some patients still may show high ventilator ‘dyssynchrony despite high levels of sedation, depending ‘on ventilator strategy. These patients may benefit from NMB to tolerate the low respiratory rates required to allow for complete exhalation, This can be facilitated by 4 bolus of cisatracuriom after adequate sedation. 754 How ido tt Infusions should be avoided to prevent myopathy from, the combination of steroids and NMB. Monitoring during NM infusions includes trin-of-four and serial creatinine kinase evaluations." Inhaled Anesthetics: Inhaled anesthetics can be used in patients with LTAE with high Ppav, excessive hypercarbia, and refractory bronchospasm who are receiving IMV. Isoflurane or halothane can reduce bbronchospastn, and evidence of improvement should be seen quickly, but only while the gases are being administered because their effect is short-lived. These anesthetics are delivered through an anesthesia, ventilator, and their use may be limited by the experience of the ICU staff. Inhaled anesthetics can cause hemodynamic instability by reducing venous and vascular tone." Extracorporeal Membrane Oxygenation: LTAE is a reversible condition in which extracorporeal membrane ‘oxygenation (ECMO) can serve as a bridge to recovery Although ECMO is required seldomly, those with severe respiratory acidosis (pH < 7.2) with hemodynamically ‘unstable DHL can benefit from it. Venovenous ECMO can be used with ultraprotective lung ventilation. As soon as bronchospasm and respiratory acidosis resolve, patients can undergo deeannulation and extubation." The use of ECMO is very limited in acute asthma, although a recent retrospective study demonstrated benefit for those who required it.” ECMO potentially can increase the risk of sepsis, multiorgan failure, acute Kidney injury, stroke, bleeding, thrombosis, and cannula-related complications. Also, its complexity ‘warrants its implementation in high-volume centers and may be cost prohibitive, and therelore may not be feasible in smaller hospital Extracorporeal CO removal is a form of extracorporeal gas exchange designed to remove CO; from the blood across a gas exchange membrane at low blood flow rates (200-1,500 mL/min). This is performed without 2 clinically relevant effect on oxygenation, as opposed to ECMO, which is used mainly for oxygen delivery at high blood flow rates (2,000-7,000 ml/min). Extracorporeal CO, removal has been referred to as low-flow ECMO and respiratory dialysis by some clinicians.” Although its role in LTAE remains to be defined, the Protective Ventilation with Veno-venous Lung Assist in Respiratory Failure (REST) tral did not find a morality benefit in patients with acute hypoxic respiratory failure compared with those receiving usual care [ 26244 enest ocrosen 2022 ]Bronchoscopy and Mucolyties: Airflow limitation in asthma results from bronchospasm, airway inflammation, and mucus plugging, but pharmacotherapy addresses only the first two causes, Bronchoscopy, BAL with or without N-acetyleysteine instilled directly into the airway, has been described as a therapeutic option in patients in whom mucus plugging is considered the main driver of airflow limitation, Conclusions ETAE is a rare complication of asthma, but if not treated in a timely fashion, it can result in death. Patients should be started quickly on inhaled SABA, short-acting muscarinic antagonists, and IV corticosteroids. Systemic infusion of magnesium sulfate ‘can be considered in some patients. In those with severe bronchospasm, heliox can be used to facilitate ‘medication delivery but therapy should be abandoned if no clinical improvement is seen after 15 min of use. Patients who have progressive respiratory distress ‘should be admitted to the ICU for close monitoring and. should be administered NIV if tolerated, However, intubation should not be delayed if the patient does not Improve in 30 to 60 min, Extra care should be taken ifa patient requires mechanical ventilation, Intubation ‘should be performed in a delayed sequence, and lung protective strategies should be adopted with IMY. Salvage therapies such as the use of inhaled anesthetics, bronchoscopy, and BAL with or without [Ne-acetyleysteine oF ECMO can be considered in individual patients with refractory disease Acknowledgments Financal/nontinancll disclosures The authors have sere to CHEST he fling N. A. HL has eceved honoraria fo sera 28 ‘connlant or air for GSK, Boring Inet Sana, Tess ‘amen, Asta Zones, and Novas Hs ination reed rece grant support fom. Asraenea, SK, San, Genesee, ovaries Bo, and ostrnger ingens. None declared (GTR) References 1 Mae, Ah: ati nd puppet Min it St yaa 2 ny, Vato, 0, Winay See cnacoe taeda eee OS an Tie samen Lae etn re 9 Ate Th i Te CE Eee et eoew 4. Danke, Ole 1, Ze A, Beane AG. A singed si ‘Store acute ska eacetain| Aaie 2015S,9.871 2, 5. Rodrigo GI. Pazing reponse a therapy in asst ath. Curr (Opn Pad Me 200815035 8 chestouraLors x 2 dig Gl Rodign CHa 8, Acte atin inal ei Che 2002S} 081-110 Taker EX, Wise SK, Marine J, Salman GA. 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