Most patients with acute asthma can be safely managed using a combination of lung-protective strategies such as lower respiratory rates and Vt, noninvasive ventilation, and the use of helium-oxygen mixtures, which can help patients avoid intubation entirely.

Ill patients with severe asthma are at risk for acute episodes of airway narrowing that are unresponsive to standard medical treatment. These life-threatening emergencies are often referred to as status asthmaticus (SA).1 Each year, acute asthma is the cause of 1 million to 2 million emergency-department visits, 450,000 hospital admissions, and approximately 5,000 deaths in the United States.2 The clinical features of the high-risk asthma patient fall into three categories: history of a previous attack, poor current disease control, and psychosocial factors compromising disease management.3 Acute, severe asthma is a state of airway inflammation and increased bronchiolar smooth-muscle tone that leads to resistance to expiration and lung hyperinflation. Due to the overexpansion of the thoracic cage, the diaphragm and intercostal muscles contract inefficiently. This elevated intrinsic positive end-expiratory pressure (PEEP) causes the acute asthma patient to use a large percentage of his or her energy to breathe. If the hyperinflation and airway obstruction are not relieved, the patient will become fatigued and progress to respiratory failure.4 Airway inflammation, mucous plugging, and smooth-muscle constriction all lead to ventilation-perfusion inequalities and to hypoxemia.3

There is significant mortality (in some reports, reaching 38%) among asthma patients requiring mechanical ventilation.5 Immediate, aggressive treatment is necessary to reduce morbidity and mortality in this patient group. Better clinical outcomes have been associated with endotracheal intubation carried out early (prior to respiratory arrest) and proper management of mechanical ventilation.5,6

The goals of mechanical ventilation are to decrease the work of breathing, maintain adequate oxygenation, and augment alveolar ventilation without causing iatrogenic harm. There are some obvious indications for intubation, such as apnea, hypopnea, and cardiopulmonary arrest. If a patient has severe dyspnea and respiratory acidosis (Paco2 >55 mm Hg and pH <7.28) despite aggressive medical treatment, it is reasonable to consider initiating mechanical ventilation.7 When a patient displays clinical deterioration, including progressive fatigue and altered mental status, intubation and mechanical ventilation should also be considered. Hypoxia and hypercapnia alone are not indications for mechanical ventilation. Mechanical ventilation has potential consequences that can contribute to mortality, including hypotension, lobar collapse, pneumomediastinum, and pneumothorax.8,9 Once the decision to intubate has been made, the oral intubation route is usually preferred because it provides the advantage of a larger airway with less resistance and permits secretion removal. It also generally causes less trauma, sinusitis, and bleeding than the nasal route.5

Effective sedation is necessary to prepare patients who are awake for mechanical ventilation, as well as to promote ventilator-patient synchrony. Sedation helps to alleviate unwanted respiratory efforts, improves patient comfort, decreases oxygen consumption, decreases carbon dioxide production, and may protect against barotrauma.1,5,7 Rapid-sequence intubation using a intravenous (IV) sedative/anesthetic agent, as well as a paralytic agent, is the preferred method of securing the airway while preventing gastric aspiration. Fentanyl, an opiate agonist, provides greater hemodynamic stability than morphine does, without the potential to cause histamine release.5 Ketamine, an IV anesthetic with analgesic, sedative, and bronchodilating properties, has been successfully used for the emergency intubation of asthma patients.1 Some of the side effects of ketamine are hallucinations (which may produce anxiety) and an increase in laryngeal secretions. Neuromuscular blockade can be used to permit controlled hypoventilation and to decrease airway pressures, oxygen consumption, and carbon dioxide production. The preferred paralytic agents are nondepolarizing agents such as vecuronium and atracurium, which have minimal cardiac toxicity. The use of atracurium, with its potential to cause the release of histamine and worsen bronchospasm, may be a problem at high doses. There is a higher incidence of acute myopathy in patients with near-fatal asthma who require muscle relaxants.1,5-8,10,11 There is some evidence from animal studies5,7 linking neuromuscular blockade and corticosteroids to this severe myopathy. The lowest effective dose should be used, and the paralytic agent should be withdrawn after the first 24 hours of treatment, if possible.

Immediately after the patient’s intubation, the clinician must be prepared for hypotension and pneumothorax. Hypotension occurs due to a combination of factors. The direct effects of sedation and loss of sympathetic activity produce a loss of vascular tone. Many patients are hypovolemic due to decreased fluid intake during the illness, as well as to insensible water loss because of increased respiratory rates. Many clinicians hyperventilate patients once an endotracheal tube is in place, leading to a decreased expiratory time, dynamic hyperinflation, and, ultimately, a decrease in blood pressure. The clinician can, instead, disconnect the resuscitation bag from the endotracheal tube and allow excessive volume to escape the lungs. Intrathoracic pressure will fall as the lungs deflate, allowing blood pressure to rise, heart rate to fall, and the pressure required to deliver subsequent breaths to decrease. If an apnea trial does not quickly restore hemodynamic stability, tension pneumothorax should be suspected. Pneumothoraces have been reported in 18% of asthma patients who require intubation.9

Ventilator Settings
Once the decision has been made to ventilate a patient mechanically, initial ventilator settings must be selected. A good understanding of the underlying pathophysiology is crucial to successful management. The rate at which an individual lung unit fills or empties is a time constant that varies according to the compliance and resistance of the lung unit. The high resistance of the asthma patient’s lung increases the time constant, leading to longer filling and emptying times. The presence of dynamic hyperinflation and the potential to cause barotrauma should be uppermost in the clinician’s mind when the ventilator is being manipulated. Volume-control ventilation and synchronized intermittent mandatory ventilation (SIMV) have traditionally been the ventilator modes of choice due to clinicians’ familiarity with them and their desire to deliver a predetermined tidal volume. In volume-control ventilation and SIMV, the constant flow (square) waveform causes more airway resistance.8,10 Often, the combination of high resistance and a short inspiratory time leads to premature termination of a volume-targeted breath, and the tidal volume that was set is not delivered. Pressure-control ventilation has been used for many years in pediatric and neonatal intensive care units. Pressure-control ventilation, with its rapid delivery of decelerating flow, is more efficient at overcoming the high resistance of the asthma patient’s lung.8,10 The decelerating flow pattern will, in most cases, decrease the peak pressure needed to deliver an identical volume as a square flow (volume) waveform breath. Distribution of ventilation should also improve as the large airways fill with the initial peak flow and the smaller airways fill with the slower flow. During pressure-control ventilation, the peak airway pressure is maintained throughout the inspiratory time, increasing mean airway pressure and, in most cases, improving oxygenation. Peak alveolar pressure is limited during pressure-control ventilation, and this may make it beneficial as a lung-protection strategy. Peak airway pressures measure both the resistive forces of the airway and the compliance forces of the lung. Plateau pressure, which is an estimate of average end-inspiratory alveolar pressures, may be the most accurate quantification of dynamic hyperinflation in the asthma patient. When plateau pressure is kept below 30 cm H2O, complications appear to be rare.1,12,13 To measure the plateau pressure, it is necessary to perform an inspiratory pause/hold while using a constant flow pattern. The main disadvantage of pressure-control ventilation is the absence of a set tidal volume. Consistent tidal volume is invaluable in maintaining consistent blood-gas levels.

New modes of ventilation called dual-control modes have evolved to deal with exactly this problem; some examples are pressure-regulated volume control, adaptive pressure ventilation, and automatically regulated inspiratory flow. These newer modes allow the patient to enjoy the clinical benefits of decelerating flow in combination with tidal-volume targeting that maintains a consistent minute volume. In addition, there is an automatic titration of the peak pressure as the patient’s compliance improves or as the patient participates in ventilation more actively. The ventilator’s active weaning of the patient, through its timely response to clinical improvement, may avert barotrauma.

Dynamic hyperinflation, which leads to worsening blood-gas levels and to potential air leaks, is directly affected by the ventilator settings chosen by the clinician. Adequate expiratory time must be provided while maintaining minimum minute ventilation. Respiratory rate, tidal volume (Vt), inspiratory flow rate, inspiratory time, and the resulting inspiratory to expiratory (I:E) ratio must be set to minimize dynamic hyperinflation. Generally, a strategy of a low minute ventilation with a high inspiratory flow rate is employed. A high inspiratory flow rate is used in many institutions to shorten the inspiratory portion of the I:E ratio and, in theory, allow more time for exhalation. The ultimate goals, however, are to lengthen absolute expiratory time, providing more time for lung emptying and for improved alveolar ventilation. This may be better accomplished through decreasing the respiratory rate set on the ventilator. For example, consider the patient with a Vt of 1 L, a respiratory rate of 15 breaths per minute, and an inspiratory flow of 60 L/min. A respiratory cycle time of 4 seconds results from these settings, with 1 second for inspiration and 3 seconds for expiration (an I:E ratio of 1:3). If the inspiratory flow for this patient is doubled, inspiratory time decreases to 0.5 seconds, expiratory time increases to 3.5 seconds, and the result is an I:E ratio of 1:7. If, instead of increasing inspiratory flow, the clinician decreases the respiratory rate from 15 to 12, that would provide 4 seconds for exhalation. The I:E ratio would be 1:4; this appears to be less favorable than the 1:7 example, but more absolute time for lung emptying has, in fact, been provided. Raising peak flow (and dramatically decreasing inspiratory time) can also elevate peak airway pressures and make it difficult to deliver the desired Vt. The asthma patient’s airway is a highly resistant one, with long time constants that require extended time periods for lung filling and emptying. High inspiratory flow rates may preferentially fill and hyperinflate more normal lung units with faster time constants.1 A high inspiratory flow may also increase mucus flow into the large airway, causing obstruction.1,13 There are also some data to suggest that high inspiratory flow rates in spontaneously breathing patients increase spontaneous respiratory rates, leading to a decrease in expiratory time.14 Using a respiratory rate of 10 to 12 breaths per minute and a Vt of 8 to 10 mL/kg to maintain a minute ventilation of less than 115 mL/kg per minute has been recommended for mechanically ventilating the asthma patient.14,15

Permissive Hypercapnia
The general management of the intubated asthma patient is based on controlled hypoventilation, without regard for hypercapnia.8 A hypoventilatory strategy diminishes the risk of severe hyperinflation. This approach allows acceptable gas exchange while minimizing the risk of barotrauma.5 Hypoventilation usually leads to hypercapnia, although a reduction in minute ventilation may allow trapped gas to be exhaled, leading to improved alveolar ventilation and a decrease in Paco2.1,14 There is good evidence that hypercarbia is well tolerated and that physiologic buffer systems should be sufficient to manage respiratory acidosis as long as the pH remains at or above 7.2.1,8,12,13 If the pH remains below 7.2, some authors5,10,12,13 recommend buffer therapy with slow infusions of either sodium bicarbonate or tromethamine, an amine buffer that does not generate carbon dioxide, but may cause hypotension, hypoglycemia, and a shift of the oxyhemoglobin dissociation curve to the left.5 The rapid infusion of bicarbonate should be avoided, as it may cause an increase in carbon dioxide production and intracellular acidosis.1 Buffer therapy may improve the patient’s tolerance for hypercapnia by reducing the drive to breathe and minimizing blood-flow and hemodynamic changes caused by acidemia.14 Hypercapnic acidosis is generally well tolerated, but it has several side effects, including cerebral vasodilation, cerebral edema, pulmonary capillary vasoconstriction, and decreased myocardial contractility.12-14 Permissive hypercapnia should not be used in individuals with increased intracranial pressures (which may occur with anoxic encephalopathy in postarrest patients). It should also be avoided in those with severe myocardial dysfunction.11-15

Numerous authors5,8,12,16,17 have reported that PEEP may benefit asthma patients by dilating airways, reducing airway resistance, and decreasing the work of breathing. The pressure applied may dilate collapsed or severely constricted airways, allowing decompression of the alveoli without an increase in alveolar pressure or lung hyperinflation.18 If no additional lung distension occurs with the addition of external PEEP, no negative hemodynamic effects should be seen.16 External PEEP may assist the patient with severe obstruction by keeping collapsible airways open and improving expiratory resistance and the distribution of ventilation.8,16 This effect is similar to that documented for pursed-lip breathing.19 For the spontaneously breathing patient, whether intubated or not, the addition of external PEEP may permit easier initiation of inspiratory flow by decreasing the gradient between the alveolar and central airway pressures. In order to trigger an assisted ventilator breath, the individual must drop the pressure in the central airways below the PEEP set on the ventilator. Even though the triggering mechanism on the ventilator may be set for relatively high sensitivity, the patient must effectively draw down through the intrinsic PEEP until the central airway pressure drops below the set PEEP. Only then will the patient be rewarded with a mechanical breath. This phenomenon helps to explain the clinical observation that some patients with severe obstruction cannot seem to trigger the ventilator, despite its extreme sensitivity and their obviously maximal efforts. The addition of external PEEP to the circuit can narrow the gradient between the central airways and the alveoli and allow more effective triggering of the ventilator. The application of external PEEP, set at or below the intrinsic PEEP level, may decrease the inspiratory threshold load imposed by intrinsic PEEP, decrease the work of breathing, and facilitate weaning the patient from mechanical ventilation.5,20 This added PEEP, if it is to decrease work of breathing and inability to trigger a breath successfully, should not add any end-expiratory lung volume. Excessive external PEEP that does add to end-expiratory lung volume will cause hyperinflation, impaired inspiratory-muscle activity, possible hemodynamic compromise, and the potential for barotrauma.8,12,16,17 One method of adding PEEP, without adding excessive lung volume, involves monitoring peak airway pressures in volume-control ventilation. If, with the addition of external PEEP, no change in peak or plateau pressure is observed, then dynamic collapse is likely and the PEEP is liable to be helpful. Exhaled Vt can be monitored during pressure-control ventilation to see if effective ventilation is affected by the increase in PEEP. Marini notes, “The use of any level of PEEP higher than the original auto-PEEP is ill advised.”16 In his own practice, he has “never added PEEP greater than 8 cm H2O for this purpose.”16

NonInvasive Ventilation
Noninvasive ventilation via face mask can improve the pathophysiology of SA and help patients avoid the dangers of intubation and mechanical ventilation. Continuous positive airway pressure (CPAP) delivered by mask decreases airway resistance, causes bronchodilation, re-expands atelectases, counterbalances intrinsic PEEP, rests the inspiratory muscles, and decreases the negative hemodynamic effects of large negative inspiratory pleural pressures.14 The addition of pressure support to CPAP can decrease inspiratory time, lengthen the available expiratory time, and facilitate lung emptying. Some other potential advantages are the decreased need for sedation and paralysis, decreased incidence of nosocomial pneumonia, and improved patient comfort.1,7,10,14 Noninvasive ventilation also has disadvantages, including decreased control of the airway with the potential risk for aspiration, pressure necrosis, patient claustrophobia due to the tight-fitting mask, and difficulty delivering aerosolized medications.1,7,10,14

Helium-oxygen mixtures
Helium-oxygen mixtures were first described by Barach21 in 1935 for the treatment of asthma. Helium is a gas of lower density than either air or oxygen. According to Poiseuille’s law, resistance to airflow through an orifice is directly related to the density of the gas. Inhalation of gas with a low density, such as helium, can reduce airway resistance and the pressure required to overcome resistance. The decreased work of breathing seen with the use of helium-oxygen mixtures may prevent respiratory muscle fatigue and help patients avoid ventilatory failure. Graham’s law states that flow will vary inversely with the square root of the density. Helium-oxygen mixtures increase expiratory flow, thus decreasing hyperinflation, airway pressure, and the risk of air leaks and hemodynamic compromise. Lowering intrinsic PEEP with a helium-oxygen mixture will reduce the threshold load on the respiratory muscles and reduce the peak airway pressures required to ventilate the asthma patient’s lung. Carbon dioxide diffuses four to five times faster through a helium-oxygen mixture than through a nitrogen-oxygen mixture, lowering the Paco2 in the hypercarbic asthma patient without increasing the peak airway pressure or respiratory rate. Airway bronchoconstriction leads to the formation of areas of low ventilation and to ventilation-perfusion inequalities within the lung. Helium-oxygen mixtures may allow ventilation to reach the areas of the lung with long time constants, improving alveolar gas exchange. In 1999, Kass and Terregino22 demonstrated, in 23 adults with acute, severe asthma who were treated with a mixture of 70% helium and 30% oxygen delivered via mask, a 25% improvement in peak expiratory flow rates and a reduction of dyspnea scores. Of these subjects, 82% showed an improvement in peak expiratory flow rates while breathing a helium-oxygen mixture (versus 17% of subjects in the control group). Kudakis et al23 studied the value of helium-oxygen mixtures in treating 18 nonintubated children (aged 16 months to 16 years) who had asthma. Pulsus paradoxus and dyspnea scores were reduced, and peak expiratory flow rates increased 69%. Mechanical ventilation was averted in three patients who would otherwise have required intubation, according to the authors. Helium-oxygen therapy for the nonintubated patient buys the time needed for other therapies to work and may, ultimately, prevent the need for intubation. For the mechanically ventilated patient, helium-oxygen mixtures may decrease airway pressures, unload intrinsic PEEP, decrease the risk of pneumothorax, improve gas exchange, and reduce the work of breathing.

In the past, the ventilator-management strategies used to treat patients with acute asthma resulted in a high risk of morbidity and mortality. Today, RCPs and physicians are gaining a better understanding of the physiological factors that cause dynamic hyperinflation and barotrauma and are improving their ventilator-management strategies, creating better outcomes for their patients. Lower respiratory rates and Vt are being used, along with the acceptance of hypercarbia. Moderate external PEEP is being added to facilitate ventilator weaning and inspiratory-muscle unloading. The judicious use of sedation and paralytic agents is decreasing ventilator asynchrony and carbon dioxide production. Information on pulmonary mechanics (including resistance, compliance, and time constants) is readily available on modern ventilators, helping the clinician make informed decisions at the bedside. Newer therapies, such as noninvasive ventilation and the use of helium-oxygen mixtures, are being used to help patients avoid intubation entirely. Most patients with acute, severe asthma can be safely managed today using a combination of these lung-protection strategies.

Melissa K. Brown, RRT, is pulmonary clinical specialist, Sharp Mary Birch Hospital For Women, San Diego. A lecture based on this text was presented at the AARC 47th International Respiratory Congress on December 3, 2001, in San Antonio.

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