A 43-years old male was admitted to our emergency depart- ment complaining of severe dyspnea. He was assigned red code and was admitted directly in shock room. The patient had hystory of asthma (but he used rarely bronchodilators) and he was a drug addict. The patient was conscious but restless, he was unable to lie down, showed signs of respiratory distress with accessory muscle use, he was unable to speak just a single word. Re- spiratory sounds were diminished on both lungs with severe diffuse and bilateral wheezing. There were no other signifi- cative findings to the physical examination. Vital signs were as follows: arterial pressure 145/80 mmHg, heart rate 140 bpm, SpO 2 70% in air. T 36,8°C, respiratory rate 40/min. Promptly, O 2 with reservoire mask was administered; a cen- tral venous line was placed in femoral vein because periferal veins were not available. The BGA showed pH 7.14 pCO 2 77 mmHg, pO 2 44.2 mmHg HCO3 28.4 mEq/l, lactate 2.8 mg/dl. The patient was administered nebulized salbutamol, iv metilprednisolone, iv aminophilline, nebulized and im epi- nephrine, iv magnesium sulphate. Because of the severe respiratory distress and the acute respiratory acidosis, we started also noninvasive ventilation by means of a Drae- ger Evita 4 ventilator with a facial mask setted as follows: PEEP 0 cmH20 (ZEEP) + ASB 8 cmH20, FiO 2 100%. The patient well tolerated noninvasive ventilation. A chest X-ray showed bilateral lung inflation without pulmonary thicken- ing or pleural effusion; cardiovascular profile was normal. (Figure 1). Blood tests showed slightly elevated neutrophil count (WBC 16730/mm3) while C-reactive protein was normal (<0,5 mg/ Case report: emergency treatment of near-fatal acute asthma Dario Lo Cigno, Federico Vischia, Antonio Sechi SC MeCAU e PS, Ospedale Torino Nord Emergenza San Giovanni Bosco, Torino L’asma bronchiale è una malattia respiratoria cronica caratterizzata da sintomi respiratori di gravità variabi- le che possono condurre all’insufficienza respiratoria. La NIV è una metodica di supporto respiratorio utilizzata da anni con successo nella BPCO riacutizzata. Tuttavia, il suo uso non è ancora ben definito nelle riacutizzazio- ni di asma bronchiale. In questo articolo presentiamo la nostra esperienza di un caso di riacutizzazione asmati- ca quasi-fatale trattata con successo in DEA mediante NIV, ed esaminiamo le evidenze scientifiche al riguardo. SINTESI dl). After 30 minutes of NIV another BGA was performed: pH 7.22, pCO 2 66 mmHg pO 2 453 mmHg HCO3 27.8 mEq/l. Clinically, the patient showed less wheezing and vi- tals signs were also improving: SpO 2 100% during NIV with FiO 2 1.0, HR 120 bpm R, PA 130/75 mmHg RR 28/min. So, we continued to ventilate the patient as described, reducing FiO 2 from 1.0 to 0.5 because of the excellent pO 2 . After 3 hours of NIV BGA was further improved (pH 7.37, pCO 2 45 mmHg, pO 2 156 mmHg, HCO3 25.4); the patient was therefore transferred in medical ward, where he was administered only O 2 -therapy with nasal cannula, broncho- dilators and steroids. He did not need ventilation anymore, and he was discharged the sixth day after admission. Noninvasive ventilation is an effective respiratory support technique, mainly in respiratory insufficiency due to COPD Fig. 1 - The patiens’ Chest x-Ray showing lung inflation. emergency care journal casi clinici em er ge nc y ca re jo ur na l - o rg an iz za zi o ne , c lin ic a, r ic er ca • A nn o V I n um er o 3 • S et te m br e 20 10 • w w w .e cj .it Materiale protetto da copyright. Non fotocopiare o distribuire elettronicamente senza l’autorizzazione scritta dell’editore. 32 exacerbations. There is increasing evidence that in patient with COPD exacerbation NIV improves blood gas tests while reducing mortality, respiratory workload, and endo- tracheal intubation needs1,3,4,5,6. Asthma is an inflammatory disease affecting small airways associated with airway hyperresponsiveness, reversible air- flow limitation, and respiratory symptoms variabile from dyspnea to status asthmaticus2. Asthma shares with BPCO some pathophysiologic features like bronchial airflow limi- tation, increased respiratory workload and increased re- sidual functional capacity, due to air trapping2. However, in asthma these features are mostly reversibile with bronchodi- lators, while in COPD they are not2. Another difference between asthma and COPD is that in latter the airway obstructed are the distal, smallest and more collapsible, while in the former the airway obstructed from mucus are the proximal ones11. Besides, in asthmatic patients the airways are stiffer than in COPD patients; so, while airway resistance is higher than in COPD, the dy- namic collapse during exhalation may be lower11. Therefore, in asthmatic patients there is a higher risk of increasing air trapping by ventilating the patient with external-PEEP with- out knowing his auto-PEEP11. This observation seems to be confermed by some pathophysiologic studies and explains why the authors recommend to ventilate asthmatic patients with zero-PEEP11,12,13. From a clinical point of view asthma exhacerbations may be divided as follows: • mild: the patient can walk, lie down and speaks almost normally; he may be agitated and respiratory rate is < 30/min14; • moderate: the patient can not lie down, can say just one sentence; he is agitated, respiratory rate is mildly in- creased but < 30/min14; • severe: the patient sits up and leans his arms on the table, he is able to speak only a few words, is agitated and re- spiratory rate is severely increased (> 30/min). When the patient became confuse or disoriented, cardiac arrest is oncoming14. In status asthmaticus, death follows asphyxia due to wors- ening respiratory distress2. This is caused by air trapping and decreased ventilation that are followed by hypoxia, hy- percapnia and acidosis2. Often, in adults, viral upper airways infection are triggers for asthma exhacerbations; however, other known triggers are psychosocial stress, exercise, and allergens2. Medical treatment of severe asthma and status asthmaticus is an important challenge for emergency physicians because therapy depends on the patient and on the degree of airflow obstruction. Asthma management includes2: • O 2 -therapy, that should be administered by any means until reaching pO 2 > 60 mmHg and SpO 2 92%; high O 2 flux may be detrimental in hypercapnic patients2. • Bronchodilators, that acts on bronchial smooth muscle reducing bronchial obstruction2: 1. beta-agonists (mainly short-acting inhaled, like salbu- tamol); they should be administered by pressurized metered-dose inhalers with spacer; as an alternative, they can be administered by nebulization in O 2 6-8 l/min. Oral or iv way of administration are not more effective, while they increase the risk of side effects (mostly arrhythmic). In severe asthma exhacerbation, beta-agonists therapy should be repeated (2.5-5 mg per dose) every 10-20 min2; 2. anticholinergics. The most effective is inhaled ip- ratropium bromide administered 80 mcg per dose by means of pressurized metered-dose inhalers with spacer. It can be repeated every 10 min2. • Corticosteroids, that act reducing airway inflammation and should be administered by 2 different ways2: 1. systemic corticosteroids, may be administered orally or iv; the recommended dose is 40-60 mg prednisone or methylprednisolone2. Probably, higher dose (> 160 mg methylprednisolone) are equally effective than lower doses2; 2. inhaled corticosteroids, that seems to increase bron- chodilator's effects2. • Theophylline. As monotherapy, theophylline is inferior to beta-agonists; however, it can give an additional bron- chodilator effect in association to beta-agonists. High in- cidence of side effects (like tachyarrhytmias) means that it may be useful only in severe asthma. Recommended loading dose is 6 mg/kg iv in 30 minutes followed by 0.5/kg/h until reaching theophylline blood levels 8-12 mcg/ml2. • Magnesium sulphate: a safe and cheap medication with some bronchodilator effect. However, 3 recent meta- analysis did not confirm its clinical effectiveness2,16,17,18. • Helium. When bronchial obstruction increases, airway flow becomes turbulent, so increasing airway resistance. Replacing nitrogen with helium (that is more viscous but equally inert) can reduce airway flow turbulence, so decreasing airway resistance. The benefits of heliox (helium + oxygen) are lost when large amounts of sup- plemental oxygen are introduced into the heliox breath- ing circuit (FiO 2 > 30% needed to maintain pO 2 > 60 mmHg)2. • Other therapies (leukotriene antagonists, antibiotics) are not effective per se but may be useful in some se- lected case2. Theoretically, COPD and asthma should respond to non-in- vasive ventilation in the same way. However, while in COPD the efficacy of non-invasive ventilation is indisputable, there is not yet an agreement on using non-invasive ventilation in asthma. In fact, some studies demostrated that NIV can reduce the need for endotracheal intubation1. In a study carried out in 2003, 30 patients were randomized in 2 groups: 15 treated with only conventional therapy, 15 treated with convention- al therapy and NIV7. After 3 h both groups showed improve- casi clinici em er ge nc y ca re jo ur na l - o rg an iz za zi o ne , c lin ic a, r ic er ca • A nn o V I n um er o 3 • S et te m br e 20 10 • w w w .e cj .it Materiale protetto da copyright. Non fotocopiare o distribuire elettronicamente senza l’autorizzazione scritta dell’editore. 33 ment in lung function tests (FEV1, FVC, PEF) and BGA pa- rameters, and decreasing in respiratory rate7. However, these parameters improve more significantly in patients treated with non-invasive ventilation7. In another study, 36 patients admitted to an emergency de- partment were randomized to 3 treatment arms: medical therapy + nebulization, and 2 treatment groups with medi- cal therapy + nebulization + NIV15. In the 2 NIV groups, inspiratory pressure was the same, while espiratory pressure was different15. The authors of this study noticed that only the group with lower espiratory pressure showed significant clinical improvement15. Another observational uncontrolled study showed an im- provement of BGA parameters, heart and respiratory rate after NIV in patient with severe asthma exhacerbations8. We can find the same results in a study on pediatric patients9. These studies suggest that in selected patients NIV may be useful as respiratory support for severe asthma. However, high power studies are lacking and in a Cochrane meta- analysis in 2005 just 1 of the 11 published studies satisfied inclusion criteria7,10. We report a case of a patient admitted for a severe asthma exhacerbation, successfully treated with optimized medi- cal therapy and NIV (zero-PEEP + pressure support). Even if anecdotical, it is not the first described in literature, be- cause some authors described similar cases and some think that NIV may be effective in these patients6,7,8. Some stud- ies agree with our hypothesis, but they are small-sized and with low statistical power15. If these data were confirmed, NIV could prevent endotracheal intubation almost in some selected patient, preventing ICU hospitalization and so de- creasing morbidity and costs. Despite that, it is not yet established if NIV could worsen dynamic hyperinflation. Besides, the higher airway resis- tance of asthmatic patient could make NIV difficult, forc- ing the physician to increase pressure support, so increasing also air losses and risk of barotrauma. Because of this point of uncertainty, and because of lacking evidence, NIV is not routinely recommended in severe asthma exhacerbations; however, the guidelines do not advise against its use2,14. So, we can conclude that further studies are needed to clarify the role of non-invasive ventilation in asthmatic patients, patients selection criteria and timing compared to invasive ventilation. References 1. Caples SM, Gay PC. Non invasive positive pressure ventilation in the in- tensive care unit: a concise review. Crit Care Med 2005; 33: 2651-2658. 2. Rodrigo GJ, Rodrigo C, Hall JB. Acute asthma in adults – a review. Chest 2004: 125; 1081-1102. 3. Brochard L, Mancebo J, Wysocki M et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med 1995; 333: 817-822. 4. Plant PK, Owen JL, Elliott MW. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on gen- eral respiratory wards: a multicentre randomised controlled trial. Lancet 2000; 355: 1931-1935. 5. Keenan SP, Sinuff T, Cook DJ et al. Which patients with acute exacerba- tion of chronic obstructive pulmonary disease benefit from noninvasive positive-pressure ventilation? A systematic review of the literature. Ann Intern Med 2003; 138: 861-870. 6. Ram FS, Picot J, Lightowler J et al. Noninvasive positive pressure ventila- tion for treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2004; 1: CD004104. 7. Soroksky A, Stav D Shpirer I. A pilot prospective, randomized, placebo- controlled trial of bilevel positive airway pressure in acute asthmatic attack. Chest 2003; 123: 1018-1025. 8. Meduri GU, Cook TR, Turner RE et al. Non-invasive positive pressure ventilation in status asthmaticus. Chest 1996; 110: 767-774. 9. Thill PJ, McGuire JK, Baden HP et al. Noninvasive positive-pressure ventilation in children with lower airway obstruction. Pediatr Crit Care Med 2004, 5: 337- 342. 10. Ram FS, Wellington S, Rowe BH, Wedzicha JA. Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbation of asthma. Cochrane Database Syst Rev 2005; 20(3): CD004360. 11. Medoff BD. Invasive and noninvasive ventilation in patients with asthma. Respir Care 2008; 53(6): 740-748. 12. Ranieri VM, Grasso S, Fiore T, Giuliani R. Auto-positive end-expiratory pressure and dynamic hyperinflation. Clin Chest Med 1996; 17(3): 379-394. 13. Tuxen DV. Detrimental effects of positive end-expiratory pressure dur- ing controlled mechanical ventilation of patients with severe airflow obstruction. Am Rev Respir Dis 1989; 140(1): 5-9. 14. Global Initiative for Asthma. A pocket guide for physicians and nurses, updated 2009 guidelines. http://www.ginasthma.org. 15. Brandao DC, Lima VM, Filho VG et al. Reversal of bronchial obstruction with bi-level positive airway pressure and nebulization in patients with acute asthma. J Asthma 2009; 46: 356-361. 16. Bourdon C, Camargo C, Bretzlaff J et al. Intravenous magnesium sulfate treatment for acute asthma in the emergency department: a systematic review of the literature. Ann Emerg Med 1999; 36: 181-190. 17. Koepsell T, Alter H, Hilty W. Intravenous magnesium as an adjuvant in acute bronchospasm: a meta-analysis. Ann Emerg Med 1999; 36: 191-197. 18. Rodrigo G, Rodrigo C, Burschtin O. Efficacy of magnesium sulfate in acute adult asthma: a meta-analysis of randomized trials. Am J Emerg Med 2000; 18: 216-221. Asthma is a chronic inflammatory disease affecting small airways, associated with hyperresponsiveness, reversible airflow-limitation and respiratory symptoms. During exhacerbations, the symptoms severity may vary from mild dyspnea to fatal status asthmaticus. Non-invasive ventilation is a respiratory support meth- od that in COPD has been used succesfully in the last 20 years; there is an increasingly interest about using non-invasive ventilation also in asthmatic patients. However, its role in status asthmaticus has not been yet established. In this article we report a case of a patient succesfully treated with non-invasive ventilation and we also review the literature about non-invasive ventilation in acute asthma ABSTRACT casi clinici em er ge nc y ca re jo ur na l - o rg an iz za zi o ne , c lin ic a, r ic er ca • A nn o V I n um er o 3 • S et te m br e 20 10 • w w w .e cj .it Materiale protetto da copyright. Non fotocopiare o distribuire elettronicamente senza l’autorizzazione scritta dell’editore. 34