Bret P. Nelson
Andy S Jagoda
The Clinical Challenge
There are a number of confounders that make airway management of the patient with asthma or chronic obstructive pulmonary disease (COPD) challenging. These patients often have difficult anatomy, are hypoxic, desaturate quickly, and can be hemodynamically unstable. Unlike many other clinical conditions, intubation itself does not resolve the primary problem, which is obstruction of the small airways. The actual intubation may be the easiest part of the resuscitative sequence because postintubation ventilation may be extremely difficult with persistent or worsening respiratory acidosis, barotrauma, or worsening hypotension caused by high intrathoracic pressures with diminished venous return. Thus, the decision to intubate must be made carefully, and the appropriate technique must be chosen to facilitate the best possible outcome.
Severe asthma often presents one of the most difficult airway management cases encountered in the emergency department. Diaphoresis is a particularly ominous sign, and the diaphoretic asthmatic patient who cannot speak full sentences, appears anxious, or is sitting upright and leaning forward to augment the inspiratory effort must not be left unattended until stabilized.
Standard initial management of acute severe asthma exacerbation includes reversal of dynamic bronchospasm using continuous beta2-agonist nebulization therapy (albuterol 15–20 mg/hour) and anticholinergic nebulization therapy (ipratropium bromide 0.5 mg per dose). In addition, oral or intravenous (IV) steroids are indicated for the treatment of the inflammatory component. If the patient is severely bronchospastic and cannot comply with a nebulized treatment, subcutaneous epinephrine or terbutaline 0.2 to 0.5 mg may be of benefit. The use of IV terbutaline is controversial; however, if selected, it should be initiated in the adult at 4 µg/kg over 10 minutes followed by a continuous infusion of 0.1–0.4 µg/kg/min, and in the child at 10 µg/kg over 30 minutes followed by a continuous infusion of 0.1 µg/kg/minute. IV albuterol can be administered at 3 µg/kg over 10 minutes followed by an infusion of 0.04 to 0.2 µg/kg/minute in the adult. The addition of inhaled or IV anticholinergic agents (atropine or glycopyrrolate), IV magnesium sulfate, IV ketamine, or inhalational helium/oxygen mixture is controversial but may be of benefit (Fig. 29-1).
In COPD, much of the obstruction is fixed, comorbidity (especially cardiovascular disease) plays a greater role, and the prognosis (even with short-term mechanical ventilation) is worse. In the patient with COPD, anticholinergic therapy may be as important as beta2-agonist therapy. Steroids are again important to attenuate underlying inflammation. Noninvasive ventilation (bilevel positive airway pressure [BL-PAP]) is of proven value in certain COPD patients and may help avoid intubation (see Chapter 38). By the time COPD patients have tired and require intubation, they have usually exhausted their catecholamine stores, are usually more hypoxic than one suspects clinically, and, like the asthmatic patient, present significant clinical challenges after intubation. There are recent reports in the literature of COPD patients in extremis who shortly after intubation became bradycardic and asystolic, and were unable to be resuscitated. The physiological explanation is not apparent. It is proposed that these patients are profoundly hypoxic before intubation, are volume depleted because of their work of breathing and their asthenic body habitus, and experience a relative sympathectomy after intubation. This condition vasodilates them globally, contributing to a decrease in cardiac output, which eventually results in cardiac arrest. These case reports, although of concern, do not reflect experience with the many COPD patients who are intubated annually and do not constitute scientific evidence regarding the incidence, cause, or treatment of this uncommon occurrence. As in the asthmatic patient, it is recommended that empiric incremental infusions of 500 mL of normal saline to a maximum of 1 to 2 L be started as soon as intubation is contemplated, and that atropine and catecholamine infusions be available before intubation.
There is no role for IV aminophylline in the management of either acute severe asthma or acute severe COPD exacerbation.
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Figure 29-1 • Approach to the Patient with Severe Asthma Exacerbation. Source: Adapted from National Heart, Lung, and Blood Institute, National Institutes of Health, National Asthma Education and Prevention Program. Expert panel report 2: guidelines for the diagnosis and management of asthma. NIH publication no. 97-4051. Bethesda, MD: U.S. Department of Health and Human Services; July 1972, and from the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2006. Available from: http://www.ginasthma.org. |
Approach to the Airway
Despite this vast array of noninvasive treatment modalities, 1% to 3% of acute severe asthma exacerbations will require intubation. These patients are usually fatigued and have reduced functional residual capacity, so it is difficult (if not impossible) to preoxygenate them optimally, and rapid desaturation must be anticipated. Because most of these patients have been struggling to breathe against severe resistance, usually for hours, they have little if any residual physical reserve, and mechanical ventilation will be required. In fact, the need for mechanical ventilation is the indication for tracheal intubation; the airway itself is almost invariably patent and protected. This fact argues strongly against awake intubation techniques, such as blind nasotracheal intubation, which take longer, exacerbate hypoxemia, and carry higher complication rates and lower success rates than rapid sequence intubation (RSI).
Technique
The single most important tenet in managing the status asthmaticus patient who requires intubation is to take total control of the airway as expeditiously as possible. Patients typically adopt an upright posture as their respiratory status worsens; this position should be maintained as much as possible during the preintubation period. Preoxygenation should be achieved to the greatest extent possible (see Chapter 3). The RSI drugs chosen should be administered to the patient in their position of comfort, often sitting upright. As the patient loses consciousness, place the patient supine, position the head and neck, and perform laryngoscopy and intubation, preferably with an 8.0- to 9.0-mm endotracheal tube to decrease resistance and facilitate aggressive pulmonary toilette. If bag-mask ventilation is required because of desaturation before intubation is achieved, Sellick's maneuver may help prevent the passage of air down the esophagus, particularly in these patients, who have high pulmonary resistance to ventilation.
Drug Dosing and Administration
If time permits, patients with reactive airways disease or obstructive lung disease should be pretreated with 1.5 mg/kg of IV lidocaine 3 minutes before induction to attenuate the reflexive bronchospasm in response to airway manipulation. Ketamine is the induction agent of choice in the asthmatic patient because it stimulates the release of catecholamines and also has a direct bronchial smooth muscle relaxing effect that may be important in this clinical setting. Ketamine 1.5 mg/kg IV is given immediately before the administration of 1.5 mg/kg of succinylcholine. If ketamine is not available, any of the other commonly used induction agents (propofol, etomidate, midazolam) may be used, but the barbiturates should be avoided as they release histamine. For COPD patients, who often have concommitant cardiovascular disease, etomidate may be preferred to avoid the catecholanine stimulation of ketamine.
Postintubation Management
After the patient is successfully intubated and proper tube position has been confirmed, sedation, paralysis if needed (see Chapter 3), and meticulous ventilator management are critical in improving patient outcome. Continuous profound sedation (and amnesia) with an appropriate benzodiazepine, accompanied by fentanyl, in analgesic doses (4–6 µg/kg, repeated as necessary) may permit optimal ventilation of the patient. For many patients, paralysis using a competitive muscle relaxant for at least the first 4 to 6 hours will prevent asynchronous respirations, promote total relaxation of fatigued respiratory muscles, decrease the production of carbon dioxide, and allow optimum ventilator settings. Additional ketamine, as well as continuous inline albuterol and other pharmacological adjuncts, may also be given.
Mechanical Ventilation
All asthmatic patients have obstructed small airways and dynamic alveolar hyperinflation with varying amounts of end-expiratory residual intra-alveolar gas and pressure (auto-positive end expiratory pressure [PEEP] or intrinsic PEEP). Elevations in auto-PEEP increase the risk for baro/volutrauma. Reversal of airflow obstruction and decompression of end-expiratory filled alveoli are the primary goals of early mechanical ventilation in the asthmatic. The former requires prompt administration of IV steroids and continuous inline nebulization with beta2-agonists until reversal is objectively measured (decrease in peak and plateau airway pressures) or unacceptable side effects are produced. Safe, uncomplicated alveolar decompression requires prolonged expiratory time (inspiration/expiration [I/E] ratio of 1:4–1:5), which is achieved by using smaller tidal volumes than usual, with a high inspiratory flow rate to shorten the inspiratory cycle time, permitting a longer expiratory phase. A general discussion of ventilation parameters can be found in Chapter 37.
The initial goal of ventilator therapy in the asthmatic patient is to improve arterial oxygen tension to adequate levels without inflicting barotrauma on the lungs or increasing auto-PEEP. Initial tidal volume should be reduced to 6 to 8 mL/kg to avoid barotrauma and air trapping. The speed at which a mechanical breath is delivered in liters per minute, typically 60 L/minute, is called the inspiratory flow (IF) rate. In asthma, the initial IF should be increased to 80 to 100 L/minute with a decelerating flow pattern. Pressure control is preferred to volume control because of the lower risk of barotrauma. If volume control is used, the operator should select the flow waveform to use ramp (decelerating) instead of square (constant). The ventilation rate should be determined in conjunction with the tidal volume, and an initial rate of 8 to 10 breaths per minute (bpm) with a high IF rate promote a prolonged expiratory phase that allows sufficient time for alveolar decompression. It is acceptable to permit the maintenance or gradual development of hypercapnia through reduced minute ventilation (the product of tidal volume and ventilatory rate) in the asthma or COPD patient because this approach reduces peak inspiratory pressure and thus minimizes the potential for barotrauma. High intrathoracic pressure may compromise cardiac output and produce hypotension; therefore, it is to be avoided.
The highest measured pressure at peak inspiration is the peak inspiratory pressure (PIP). The patient's lungs, chest wall, endotracheal tube, ventilatory circuit, ventilator, and mucus plugs all contribute to the PIP. This reading has an inconsistent predictive value for baro/volutrauma, but ideally should be kept under 50 cm H2O. A sudden rise in PIP should be interpreted as indicating tube blockage, mucous plugging, or pneumothorax until proven otherwise. A sudden, dramatic fall in PIP may indicate extubation.
The measured intra-alveolar pressure during a 0.2- to 0.4-second end-inspiratory pause is referred to as the plateau pressure (Pplat). Values <30 cm H2O are best and are not usually associated with baro/volutrauma. Measurement and trending of Pplat is an excellent objective tool to confirm optimal ventilator settings and the patient's response, as well as the reversal of airflow obstruction. If initial ventilator settings disclose a Pplat of more than 30 cm H2O, consider lowering minute ventilation and increasing IF, both of which will prolong expiratory time and attenuate hyperinflation. If Pplat is unavailable, PIP may be used as a surrogate.
Most status asthmaticus patients who require intubation are hypercapnic. The concept of controlled hypoventilation (permissive hypercapnia) promotes gradual development (over 3–4 hours) and maintenance of hypercapnia (Pco2 up to 90 mm Hg) and acidemia (pH as low as 7.2). This treatment is done primarily to decrease the risk of ventilator-related lung injury and prevent hemodynamic compromise as a result of increasing intrathoracic pressure from auto-PEEP or intrinsic PEEP. Permissive hypercapnia is usually accomplished by reducing minute ventilation, increasing inspiratory flow rate to 80 to 120 L/minute, and heavily sedating (and usually paralyzing) patients who otherwise would not tolerate these settings. Permissive hypercapnia may be instrumental in promoting prolonged expiratory times and reducing auto-PEEP.
Summary for Initial Ventilator Settings
1. Determine the patient's ideal body weight.
2. Set a tidal volume of 6 to 8 mL/kg with a FiO2 of 1.0 (100% oxygen).
3. Set a respiratory rate of 8 to 10 bpm.
4. Set an inspiratory-to-expiratory (I/E) ratio of 1:4 to 1:5. Pressure control is preferred. If using pressure control, the I/E ratio is adjusted directly by the I/E ratio parameter or by adjusting the inspiratory time parameter. If using volume control, the I/E ratio can be adjusted by increasing the peak flow rate, and the ramp inspiratory waveform should be selected. Peak inspiratory flow can be as high as 80 to 100 L/minute.
5. Measure and maintain the plateau pressure at <30 cm H2O; try to keep PIP at <50 cm H2O.
6. Focus on the oxygenation and pulmonary pressures initially. If necessary, allow maintenance or gradual development of hypercapnia to avoid high plateau pressures and increasing auto-PEEP.
7. Ensure continuous sedation and analgesia with a benzodiazepine and a nonhistamine releasing opioid, such as fentanyl, and consider paralysis with a nondepolarizing muscle relaxant if it is difficult to achieve ventilation goals (see Chapter 3).
8. Continue inline beta2-agonist therapy and additional pharmacological adjunctive treatment based on the severity of the patient's illness and objective response to treatment.
Complications of Mechanical Ventilation
Two of the more common complications seen in mechanically ventilated asthmatic patients are lung injury (baro/volutrauma) and hypotension. Lung injury is exemplified by tension pneumothorax. In those patients without tension pneumothorax, hypotension is usually related to either absolute volume depletion or relative hypovolemia caused by decreased venous return from increasing auto-PEEP and intrathoracic pressure. The inherent risks of developing either one of these complications are directly related to the degree of pulmonary hyperinflation. Of the two, hypotension occurs much more frequently than tension pneumothorax. Most asthmatic patients will have intravascular volume depletion because of the increased work of breathing, decreased oral intake following the onset of asthmatic exacerbation, and generalized increased metabolic state. It is appropriate for these reasons to infuse up to 2 L of normal saline (NS) either before the initiation of RSI or early during mechanical ventilation.
The differential diagnosis for hypotension in the mechanically ventilated patient is discussed in Chapter 3. A trial of hypoventilation (apnea test) may be used to distinguish tension pneumothorax from volume depletion. The patient is disconnected from the ventilator and allowed to be apneic up to 1 minute as long as adequate oxygenation is ensured by pulse oximetry. In volume depletion, the mean intrathoracic pressure will fall quickly, blood pressure should begin to rise, pulse pressure will widen, and pulse rate will fall within 30 to 60 seconds. If auto-PEEP is high, reductions in tidal volume and increases in inspiratory flow and I/E times will be required to reduce auto-PEEP. If auto-PEEP is not an issue, then an empiric volume infusion of 500 mL NS should be instituted and may be repeated based on the patient's response to the additional volume. With tension pneumothorax, cardiopulmonary stability will not correct during the apnea time. This result should prompt the immediate insertion of bilateral chest tubes and re-evaluation of the patient. Obviously, lower ventilatory pressure settings will be required thereafter. The initial ventilator settings and potential ventilator complications of the asthma patient are shared by the COPD patient.
Evidence
1. Does lidocaine improve clinical outcomes when patients with status asthmaticus are intubated? Intravenous lidocaine has been recommended in the literature to attenuate airway reflexes during intubation in patients with reactive airway disease (1,2). Stimulation of the airway in asthmatic patients is reported to result in bronchoconstriction, which is believed to be mediated via the vagus nerve (3). The recommendation to use IV lidocaine in RSI protocols for the severe asthmatic is extrapolated from the results of studies using healthy volunteers with a history of bronchospastic disease (4,5,6). In one double-blind, placebo-controlled randomized study, volunteers who had a demonstrated decrease in forced expiratory volume (FEV1) in response to histamine inhalation were shown to have a significant attenuation of response when pretreated with IV lidocaine (5). Unfortunately, there is also evidence that IV lidocaine does not protect against intubation-induced bronchoconstriction in asthma. In a prospective randomized double-blind, placebo-controlled trial of 60 patients, lidocaine and placebo groups were not different in their transpulmonary pressure and airflow immediately after intubation and at 5-minute intervals (7). The same study evaluated inhaled albuterol (four puffs from a metered dose inhaler [MDI] 20 minutes before intubation), which showed significant mitigation of intubation-induced bronchospasm. There are no studies that have demonstrated that premedicating with IV lidocaine in RSI changes outcome; conversely, there is no evidence that premedication with IV lidocaine is harmful. Until better data are available, it seems reasonable to minimize the risk of intubation-induced bronchoconstriction by using lidocaine premedication in the asthmatic.
2. Do inhaled anticholinergics improve outcomes in acute reactive airways disease when compared to inhaled beta-agonists alone? The bronchodilatory effects of anticholinergic agents are well known, but there has been controversy over whether these agents act synergistically with beta-agonists in the setting of acute bronchospasm. A recent meta-analysis of the role of ipratropium bromide in the emergency management of acute asthma exacerbation concluded that there is a modest benefit when it is used in conjunction with beta-agonists (8). Thirty-two randomized controlled trials enrolling 3,611 subjects were included. The use of inhaled anticholinergics was associated with reduced hospital admissions in adults and children, as well as improved spirometric parameters within 2 hours of treatment. For severe asthma exacerbations, the number needed to treat to prevent one admission was 7 for adults and 14 for children. The meta-analysis recommended the use of inhaled ipratropium bromide because the benefit appears to outweigh any risks. In addition, pooled data suggest that multiple doses convey more benefit than single-dose regimens. A recent prospective, double-blind, randomized controlled trial examined the benefit of adding continuous nebulized ipratropium bromide to a continuous albuterol nebulization (9). In this study, the addition of ipratropium bromide was not found to improve peak expiratory flow rate (PEFR) or admission rates compared to albuterol alone in a total of 62 enrolled patients. Theoretically, in status asthmaticus where inhaled agents have limited delivery, IV anticholinergic agents may have benefit (10). However, other than case reports, there is no evidence at this time supporting their use. There is strong evidence for the long-term use of anticholinergic agents in the routine management of COPD (11,12,13,14). Use in acute exacerbations has been less well studied; a Cochrane Database review summarized four studies comparing inhaled albuterol with ipratropium bromide in the setting of acute COPD exacerbation (15). Pooled data from these studies (129 total patients) demonstrated no difference in FEV1 at 1 hour or 24 hours between the albuterol and ipratropium bromide groups. The addition of ipratropium bromide to albuterol did not yield any benefit over albuterol alone. Despite this relative paucity of evidence, the American Thoracic Society and European Respiratory Society (16) and the Global Initiative for Chronic Obstructive Lung Disease (17) advocate the use of inhaled ipratropium in acute COPD exacerbations. Thus, based on available evidence, anticholinergic agents should be used in acute asthmatic patients as standard therapy and should be considered in the treatment of acute COPD exacerbations, especially when little improvement is seen with beta-agonists alone.
3. Does the use of IV magnesium improve outcomes in patients with acute asthma? Magnesium plays a role in smooth muscle relaxation, and recent research has focused on the role of this medication in alleviating bronchospasm. Several meta-analyses have examined the role of magnesium in acute asthma (18,19). Pooled data do not demonstrate significant improvement in PEFR or admission rates with the administration of IV magnesium. However, in a subgroup analysis of patients with severe asthma (defined as PEFR of 25% to 30% of predicted for adults or failure to improve beyond 60% predicted after 1 hour of care for children), IV magnesium improved PEFR by 9.8% predicted and reduced hospital admission rates. There is no good evidence that in severe asthma, magnesium decreases the need for intubation. Recently, a systematic review examining the role of nebulized magnesium demonstrated a benefit in pulmonary function in severe asthma (20). No benefit (vs. standard therapy) was seen in less severe cases, and no subgroup experienced a decreased rate of hospital admission. Based on these data, IV magnesium therapy should be considered as adjunctive therapy only in selected cases of severe asthma.
4. Are there any noninvasive ventilatory strategies that may improve respiratory status in acute asthma? Noninvasive positive-pressure ventilation has demonstrated a bronchodilatory effect in methacholine-induced bronchospasm (21,22), and it has been postulated that the addition of positive pressure may offset intrinsic PEEP and decrease work of breathing. However, few studies have examined the role of noninvasive positive-pressure ventilation in the setting of acute asthma. In a prospective, randomized cross-over study of 20 pediatric intensive care unit (ICU) admissions, BL-PAP use for 2 hours decreased respiratory rate, accessory muscle use, wheeze, and dyspnea (23). A 2003 emergency department study randomized 15 adult patients to BL-PAP and 15 to standard therapy for a 3-hour treatment period (24). The BL-PAP group demonstrated fewer hospital admissions, improved respiratory rate, and improved PEFR and FEV1. There were no cases in either study of pneumothorax. Based on these limited data, it would be reasonable to consider BL-PAP for more severe cases of acute asthma, when immediate intubation does not appear to be required.
5. Is there a role for heliox in the management of acute asthma or COPD exacerbations? In obstructive lung disease with bronchospasm, increased turbulent flow through proximal airways decreases airflow and may contribute to increased work of breathing. Heliox, with a lower density than air-oxygen mixtures, has been believed to decrease turbulent flow and could increase carriage of nebulized medications to distal airways. A recent systematic review examined controlled studies of acute asthma and COPD exacerbations (25). For asthma, heliox-driven nebulizers improved PEFR in pooled data from two studies. No differences in admission rates were found. Heliox was found in a single study to improve PEFR when used as a breathing gas in intubated asthmatics. In COPD, heliox-driven nebulizers did not change PEFR compared with controls. When used in conjunction with noninvasive ventilation, heliox did not improve Pco2, change intubation rates, or decrease length of stay in the ICU. There was a decreased overall hospital length of stay in the heliox group, however. In intubated COPD patients, heliox used as a breathing gas demonstrated a reduction in intrinsic PEEP of 2.2 cm H2O compared to controls and improved work of breathing, but did not affect other outcomes. There is one case series of seven intubated patients with elevated airway pressures who had remarkable improvement with a 60 to 40 helium/oxygen mixture; however, this is a case series and thus suffers from inherent bias, precluding recommendations (26). At this time, there is insufficient evidence of outcome benefit to justify the cost and complexity of heliox administration.
6. Is IV ketamine of benefit in severe asthma? Theoretically, ketamine is a logical choice in managing the airway of the severe asthmatic because it increases circulating catecholamines, it is a direct smooth muscle dilator, it inhibits vagal outflow, and it does not cause histamine release (27). However, there are no good controlled studies demonstrating the benefit of IV ketamine in the management of the nonintubated asthmatic. Case reports of dramatic improvement in pulmonary function with ketamine have driven its popularity (28,29), but no randomized studies have been performed to demonstrate ketamine's superiority over other agents. In a case series, 19 of 22 actively wheezing asthmatics had a decrease in bronchospasm during ketamine-induced anesthesia (30). In one prospective double-blind, placebo-controlled trial of 14 mechanically ventilated patients with bronchospasm, the 7 patients treated with ketamine (1 mg/kg) had a significant improvement in oxygenation but no improvement in Pco2 or lung compliance. Outcome (discharge from the ICU) was the same in both groups. The study population was heterogeneous, making conclusions of the benefit of ketamine difficult at best (31). A randomized double-blind, placebo-controlled trial of low-dose IV ketamine, 0.2 mg/kg bolus, followed by an infusion of 0.5 mg/kg/hour in nonintubated adult patients with acute asthma failed to demonstrate a benefit from IV ketamine (32). The incidence of dysphoric reactions led the investigators to decrease the bolus to 0.1 mg/kg. Recently, a double-blind, placebo-controlled study randomized 33 pediatric asthma patients to ketamine infusion (0.2 mg/kg bolus, followed by 0.5 mg/hour for 2 hours) and 35 patients to placebo (33). Each group also received albuterol, ipratropium bromide, and glucocorticoids. No significant difference in pulmonary index scores (comprised of respiratory rate, wheeze, I/E ratio, accessory muscle use, and oxygen saturation) were found between the two groups. No difference in hospitalization rate was noted. At the present time, based on its mechanism of action and safety profile, ketamine appears to be the best agent available for RSI in the asthmatic. In the absence of ketamine, other agents may be used. There is insufficient evidence to support the use of IV ketamine as adjunctive therapy in nonventilated patients.
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