Patients with severe acute asthma exacerbations should be promptly and aggressively managed in the emergency department with inhaled β-agonist agents, inhaled ipratropium bromide, oxygen, and a systemic corticosteroid. Patients who fail to improve or who further deteriorate should be admitted to the intensive care unit for escalation of therapy and a higher level of monitoring.
Standard treatments include administration of intravenous fluids, oxygen, β-agonist agents by intermittent or continuous nebulization, ipratropium bromide, parenteral corticosteroids, and intravenous infusion of a β 2 -agonist agent. Other therapies available in the intensive care unit include intravenous infusions of magnesium sulfate and methylxanthine agents, and breathing helium-oxygen mixtures.
Failure to respond to treatment can lead to further deterioration and the development of respiratory failure, necessitating noninvasive ventilatory support or even intubation and mechanical ventilation. When needed, ventilation should be initiated with a strategy that avoids dynamic hyperinflation. Select patients may benefit from inhalational anesthetic agents for bronchodilation, bronchoscopy to relieve airway obstruction or atelectasis resulting from mucous plugging, or extracorporeal life support.
Aggressive medical treatment and a mechanical ventilation strategy that minimizes dynamic hyperinflation result in low morbidity and near-zero mortality rates in patients with critical or near-fatal asthma.
Asthma is a highly prevalent chronic disease that affects both children and adults. It is the most common medical emergency in the pediatric population. Despite adequate treatment and access to medical care, patients with asthma are at risk for episodic acute respiratory deterioration, commonly known as reactive airway disease exacerbations or asthma attacks. These episodes vary greatly in severity, ranging from those that are easily managed in the outpatient setting by increasing corticosteroid and bronchodilator therapy to severe episodes with intense airway obstruction that rapidly evolve to respiratory failure.
Several terms are used to denote severe asthma attacks, including status asthmaticus , acute severe asthma , critical asthma , and near-fatal asthma . Definitions vary among sources; many consider status asthmaticus to be an outdated term. For this text, acute severe asthma is defined as an asthma attack unresponsive to repeated doses of β-agonists and requiring hospital admission , ; critical asthma is defined as acute severe asthma necessitating intensive care unit (ICU) admission ; and near-fatal asthma is defined as critical asthma that requires endotracheal intubation and mechanical ventilation.
Epidemiology and risk factors
Asthma is the most common chronic illness in childhood, affecting 9.5% of all children in the United States. Overall global prevalence is approximately 11% to 13% and varies widely, from approximately 5% in some Asian and Eastern Europe countries to nearly 25% in parts of Central America, South America, Oceania, and the United Kingdom. The prevalence of asthma increased worldwide between 1990 and 2015. Asthma is a common reason for hospitalization, with approximately 3 million pediatric asthma exacerbations and 150,000 pediatric asthma admissions occurring in the United States annually. , It is also a common comorbidity among children hospitalized for other reasons, present in 21.8% of all-cause pediatric hospitalizations. In some countries, including the United States, asthma hospitalizations are becoming less frequent, but admissions are increasing in other developed countries. , , Even in areas where the incidence of acute severe asthma is decreasing, admissions to the pediatric ICU (PICU) are increasing. In New Jersey, the incidence of critical asthma increased from 0.09 to 0.31 per 1000 children between 1992 and 2006, and 35% of acute severe asthma admissions received ICU care during the final years of the study period. In Ohio, ICU utilization averages approximately 25% among six children’s hospitals, with greater than 40% of hospitalized children receiving ICU care at some centers. Rates of positive-pressure ventilation for asthma have increased recently in the United States and Spain. , Among critical asthma patients in the United States, 5% to 12% are treated with invasive mechanical ventilation, and 3% to 5% are treated with noninvasive ventilation. , , Intubation may occur prior to PICU admission and is associated with shorter duration of mechanical ventilation. Despite this increase in critical care utilization, mortality rates from acute severe asthma (<0.1%), critical asthma (∼0.3%), and near-fatal asthma (∼4%) are quite low. Many of the deaths from asthma occur in patients who experienced prehospital cardiac arrest. , , ,
Risk factors for severe asthma exacerbations are of particular importance to the practicing intensivist ( Box 50.1 ). Critical asthma is disproportionately more common in boys, impoverished regions, Hispanic children, and African-Americans. , Risk factors for near-fatal asthma include African-American race, older age, concurrent pneumonia, and the presence of comorbid conditions. , ,
Previous asthma attack with:
Admission to intensive care unit
Respiratory failure and mechanical ventilation
Seizures or syncope
Pa co 2 >45 torr
High consumption (>2 canisters per month) of β-agonist metered-dose inhalers
Underuse of corticosteroid therapy
Denial of or failure to perceive severity of illness
Associated depression or other psychiatric disorder
Dysfunctional family unit
Nonwhite children (black, Hispanic, other)
The majority of patients with asthma who progress to near-fatal asthma or cardiac arrest do so prior to arrival at the emergency department or during the first stages of therapy. , Therefore, early identification and close monitoring of patients at high risk for near-fatal asthma could be advantageous. High-risk patients often have a history of ICU admissions, , mechanical ventilation, , seizures or syncope during an attack, Pa co 2 greater than 45 torr, , attacks precipitated by food, atopy, or a history of rapidly progressive and sudden respiratory deterioration. High-risk patients are likely to use more than two canisters of β-agonist metered-dose inhalers per month and often are poorly compliant or are receiving insufficient steroid therapy. , Denial or imperception of the severity of an attack are factors frequently associated with near-fatal asthma. , Although, unquestionably, some patients at risk for near-fatal asthma simply ignore early warning signs and do not seek medical attention, a subgroup of patients actually lacks normal perception of disease severity. Some patients with near-fatal asthma exhibit reduced chemosensitivity to hypoxia and blunted perception of dyspnea. Other patients have a decreased perceptual sensitivity of inspiratory muscle loads and display abnormal respiratory-related evoked potentials.
Although many of these high-risk factors are commonly present in patients with near-fatal asthma, they fail to identify a significant number of cases. In one case series, 33% of patients who died of asthma were judged to have a history of trivial or mild asthma, whereas 32% had never been admitted to the hospital with an asthma exacerbation. More recently, the Collaborative Pediatric Critical Care Research Network reported that 13% of 260 children with near-fatal asthma had no prior history of asthma and that only 37% of known asthmatics had required hospitalization in the 12 months preceding the episode of near-fatal asthma. Some of these patients may, in fact, have what likely represents a distinct clinical entity known as sudden asphyxial asthma, a condition marked by acute onset of severe airway obstruction and hypoxia that rapidly leads to cardiorespiratory arrest in patients known to have only mild asthma or no asthma history at all.
Asthma is primarily an inflammatory disease. As such, it is marked by highly complex interactions among inflammatory cells, mediators, and the airway epithelium ( Fig. 50.1 ). Functionally, asthma is characterized by variable airflow obstruction and airway hyper-responsiveness associated with airway inflammation and may represent a spectrum of unique pathophysiologic phenotypes and endotypes. Though various phenotypes cause clinical asthma, asthmatic patients commonly have airway inflammation dominated by eosinophils, T H 2 cytokines, and immunoglobulin E (IgE). Pathologically, it is marked by mast cell degranulation, accumulation of eosinophils and CD4 lymphocytes, hypersecretion of mucus, thickening of the subepithelial collagen layer, and smooth muscle hypertrophy and hyperplasia.
Mast cells, eosinophils, neutrophils, macrophages, and T lymphocytes are central to the derangements that occur during an acute attack (see Fig. 50.1 ). The usual cascade begins with the activation and degranulation of mast cells in response to allergens or topical insults. Mast cells release mediators—including histamine, prostaglandins, and leukotrienes—that cause acute bronchoconstriction. Additionally, the mast cells promote activation of T lymphocytes via allergen presentation. The inflammatory process is then amplified by T-lymphocyte release of cytokines and chemokines, predominantly T H 2 cytokines, such as interleukin (IL)-4, IL-5, IL-8, and IL-13. The presence of these T H 2 cytokines leads to further augmentation of the inflammatory process through excessive production of IgE by B cells, stimulation of airway epithelial cells, and eosinophil chemotaxis. IgE stimulates mast cells to release leukotrienes, whereas interleukins (particularly IL-5) promote maturation and migration of activated eosinophils into the airway. This highly inflammatory state results in stimulation of airway epithelial cells and continued augmentation of the inflammatory process by further release of leukotrienes, prostaglandins, nitric oxide (NO), adhesion molecules, and platelet-activating factor. This process results in overproduction of mucus and in epithelial cell destruction that lead to airway plugging and denuding of the airway surface. Disruption of the epithelial surface exposes nerve endings, resulting in hyperirritable airways that become more susceptible to spasm and obstruction when challenged by subsequent exposures to allergens and irritants. Airway irritants that trigger acute asthma include cigarette smoke and inhaled particulates, respiratory tract viruses, psychological stress, and cold air. The mucus secreted in the airways of asthmatics contains large amounts of cellular debris and is thicker than in normal persons. Mucus hypersecretion may be a principal cause of respiratory failure in persons with severe asthma and has been underappreciated as a factor in respiratory failure.
Ultimately, inflammation-mediated airway edema, mucus hypersecretion, airway plugging, and bronchospasm lead to the severe airway obstruction seen in patients with severe asthma exacerbations. The resulting obstruction and increased airway resistance create an impediment for inspiratory and expiratory gas flow, which leads to deranged pulmonary mechanics and increased lung volumes.
Airway plugging can result in ventilation/perfusion mismatching and an increased oxygen requirement. Hypoxemia is nearly universal in patients with a severe asthma attack, but generally it is easily corrected with supplemental oxygen and is only weakly correlated with pulmonary function abnormalities. More frequently, heterogeneous airway plugging and obstruction lead to regional alveolar hyperinflation associated with reduced perfusion, resulting in a significantly increased pulmonary dead space. Most patients with acute asthma exhibit an increased respiratory rate in an attempt to achieve a higher minute volume and compensate for the ventilation abnormality. In asthmatics with acute exacerbations, airway obstruction results in significant prolongation of expiratory time. The subsequent breath is initiated before the last one has emptied, leading to dynamic hyperinflation. The small airways collapse and close at a higher than normal lung volume, contributing further to air trapping. At higher lung volume, there is a higher alveolar driving pressure to empty the lung, which should serve as an adaptive mechanism. However, the net result in acute asthma is high-energy use. Expiration becomes active with the use of the abdominal muscles. At high lung volumes, the lung is less compliant and the inspiratory accessory muscles are engaged to help move an adequate tidal volume. ,
During a severe attack, inspiratory transpulmonary pressures in excess of 50 cm H 2 O may be generated compared with approximately 5 cm H 2 O during normal breathing. The increased muscle work is accompanied by an increase in blood flow to the diaphragm, but this flow often is insufficient to meet the much greater metabolic demands. Failure to promptly relieve the airway obstruction and reduce the work of breathing eventually lead to respiratory muscle fatigue, inadequate ventilation, and respiratory failure.
States of advanced airway obstruction and dynamic hyperinflation typical of severe asthma attacks have a significant impact on the circulatory system. The highly negative intrapleural pressures generated by spontaneously breathing patients during inspiration favor transcapillary fluid movement into the interstitium and air spaces, promoting pulmonary edema. They also cause a phasic increase in left ventricular afterload and a decrease in cardiac output that is clinically manifested as pulsus paradoxus. Right ventricular afterload may be increased during severe asthma because of pulmonary vasoconstriction related to hypoxia and acidosis. A state of increased pulmonary vascular resistance resulting from dynamic hyperinflation also can increase right ventricular afterload, further affecting cardiac output.
The child with an asthma exacerbation usually presents with complaints of difficulty breathing and shortness of breath. The presence of these complaints in a child known to have had previous asthma exacerbations is highly suggestive of the diagnosis. A significant percentage of children have a history of a coexisting viral upper respiratory infection, whereas some describe exposure to known allergic triggers. Circumstances permitting, one should inquire about the presence of high-risk factors (see earlier section) for severe disease and the adequacy of maintenance therapy.
Children with severe forms of acute asthma commonly present with tachypnea, diaphoresis, increased use of accessory muscles, and nasal flaring. Sick nonverbal children may appear anxious, agitated, or simply unable to be distracted from the task of breathing. Speech in older children occurs in short phrases because of the rapid respiratory rate. The presence of intercostal, subcostal, and suprasternal retractions; nasal flaring; inability to speak in full sentences; and agitation are signs of impending respiratory failure. Evolution or persistence of these signs is followed by slower labored breathing, confusion or obtundation, and respiratory arrest.
Wheezing, which is a common clinical finding in patients with acute asthma exacerbations, is the audible manifestation of turbulent airflow in the intrathoracic intrapulmonary airways. Wheezing is usually expiratory as a result of the dynamic compression of conducting airways, but it can be inspiratory as well. Wheezing in persons with severe asthma usually is bilateral. Asymmetric wheezing suggests regional mucous plugging, atelectasis, pneumothorax, or the presence of a foreign body. The degree of wheezing correlates poorly with disease severity because wheezes are heard only in the presence of sufficient airflow. A patient with severe airway obstruction and very limited airflow may have a silent chest upon initial examination, but loud wheezes may develop after effective therapy. Likewise, in a patient with loud wheezes who continues to worsen, a reduction in wheezing may occur as a prelude to respiratory failure.
An objective assessment of disease severity is important in evaluating a patient’s response to therapy. Several asthma severity scores are widely used in clinical practice, including the Clinical Asthma Score, Pediatric Asthma Severity Score, Acute Asthma Intensity Research Score, and the Preschool Respiratory Assessment Measure. Wood and colleagues developed a practical clinical asthma score specifically intended to identify near-fatal asthma. It is composed of five variables with three different grades that allow for semiquantitative assessment of disease severity ( Table 50.1 ) and correlates well with the need for prolonged bronchodilator therapy and hospitalization. Increasing scores correlate with progressive hypercarbia, and scores greater than 5 often indicate respiratory failure. However, although clinical asthma scores seem to be useful for assessing the severity of an attack, they are not as effective in prospectively identifying patients who require prolonged hospitalization or in whom complications and subsequent disability develop. , There is still a need for a single scoring system with sufficient validity, reliability, and utility for universal clinical application.
|Pa o 2 (torr) or||70–100 in 21% O 2||<70 in 21% O 2||<70 in 40% O 2|
|Cyanosis||None||In 21% O 2||In 40% O 2|
|Inspiratory breath sounds||Normal||Unequal||Decreased to absent|
|Accessory muscles used||None||Moderate||Maximal|
|Cerebral function||Normal||Depressed or agitated||Coma|
A less frequently used but more objective method of assessing disease severity and progression in patients with severe asthma is measurement of the pulsus paradoxus. Originally described by Adolf Kussmaul in a patient with constrictive pericarditis, pulsus paradoxus also is observed in conditions in which pleural pressure swings are exaggerated, such as critical asthma. The simplest definition of pulsus paradoxus is an exaggeration of the physiologic inspiratory decrease in systolic blood pressure ( Fig. 50.2 ). Several mechanisms have been proposed for the occurrence of pulsus paradoxus in persons with asthma. It is likely that various mechanisms contribute differently depending on the adequacy of intravascular volume, magnitude of pleural pressure swings, degree of pulmonary hyperinflation, and state of cardiac contractility. These mechanisms include cyclic increases in left ventricular afterload and in venous return to the right heart from highly negative intrapleural pressure during inspiration ; decreased left ventricular preload as a result of inspiratory blood pooling in the pulmonary vasculature ; impaired left ventricular diastolic filling caused by a leftward shift of the interventricular septum resulting from increased venous return to the right heart ; constraint of cardiac filling because of longitudinal inspiratory deformation of the pericardium ; and increased right ventricular afterload with decreased filling of the left ventricle as a result of hyperinflation, acidosis, and hypoxia. The pulsus paradoxus can be measured easily in a patient who is spontaneously breathing by transducing pressure signals from an indwelling arterial catheter. Alternatively, it can be measured with a manual sphygmomanometer by inflating the cuff 20 mm Hg above the systolic pressure and then deflating it slowly until the first Korotkoff sounds are heard (systolic blood pressure). Initially, Korotkoff sounds are heard only during expiration. The cuff is then carefully deflated until the point at which the sounds are appreciated during both inspiration and expiration and correspond to every heartbeat. The difference between the highest systolic pressure and the pressure at which all Korotkoff sounds are heard is the magnitude of the pulsus paradoxus. During normal breathing, this difference is less than 5 mm Hg, but it is generally greater than 10 mm Hg during acute asthma exacerbations and greater than 20 mm Hg in patients with more severe disease. Changes in the magnitude of pulsus paradoxus during the course of therapy are good indicators of disease severity and clinical response to treatment. ,
A chest radiograph is not routinely indicated in acute severe asthma but may be useful in patients suspected of having a pneumothorax, pneumomediastinum, pneumonia, pulmonary edema, cardiomegaly, or clinically important atelectasis. In children presenting with a first episode of severe wheezing, a chest radiograph may help diagnose anatomic abnormalities (such as vascular rings or a right-sided aortic arch) or foreign bodies. We generally obtain a chest radiograph in patients who are sick enough to require monitoring and treatment in the ICU to exclude the possibility of additional extrapulmonary or airspace diseases. In our practice, this has revealed conditions such as mediastinal tumors, congestive heart failure, and anomalous left coronary artery in children diagnosed with asthma in the pre-ICU setting.
Arterial blood gas analysis
Arterial blood gas measurements provide objective information on the adequacy of ventilation and oxygenation of the patient with asthma. The typical blood gas abnormality in the early phase of acute asthma is hypoxemia with hypocapnia (partial pressure of carbon dioxide [Pa co 2 ] <35 torr), reflecting hyperventilation. With worsening airway obstruction, Pa co 2 measurements return to the normal range of approximately 40 torr. However, this “normal” Pa co 2 should not be viewed as reassuring when taken in the context of prolonged expiratory time, tachypnea, and accessory muscle use. In fact, Pa co 2 greater than 40 torr in a patient with a severe asthma exacerbation should be interpreted as a sign of evolving respiratory muscle fatigue and warrants close clinical observation. Sicker patients often exhibit a mixed respiratory and metabolic acidosis. Lactic acidosis is frequently encountered in these patients and usually is secondary to excess sympathetic stimulation (type B lactic acidosis), though it may also reflect tissue hypoxia and impending respiratory failure. Measurement of the lactate/pyruvate ratio may help distinguish the etiology of lactic acidosis.
Abnormal arterial blood gas measurements alone should not be the basis for the decision of whether to intubate a child with asthma. Intubation should be dictated by the overall clinical status and may come before blood gas aberrations reach the criteria for respiratory failure used in other diseases. In children requiring mechanical ventilation, frequent blood gas measurements are essential to monitor disease progression and the adequacy of ventilatory support. Additionally, blood gas analysis may be the only means to diagnose significant hypercarbia in critical asthma patients who have neurologic comorbidities or static encephalopathy and those receiving sedative medications.
Electrolytes and complete blood cell count
Routine blood chemistry analysis and blood cell counts generally are not helpful in patients with acute severe asthma. Children who present with a protracted asthma attack may have evidence of dehydration with elevated blood urea nitrogen or decreased bicarbonate because of inadequate oral fluid intake and increased insensible water losses. Patients undergoing repeated treatments with nebulized or intravenous (IV) β – agonist agents might show evidence of hypokalemia from the potassium shift to the intracellular space. The white blood cell count usually is normal, although some atopic patients may exhibit elevated eosinophil counts. The presence of leukocytosis does not necessarily indicate infection and often is related to adaptive stress or the administration of exogenous corticosteroids. As with chest radiography, many intensivists routinely obtain laboratory analysis at PICU admission to evaluate for additional diagnoses beyond asthma.
Myoglobin, a heme protein present in skeletal and cardiac muscle, is often elevated in patients with near-fatal asthma. At least one-third of patients with acute severe asthma exhibit an elevated plasma creatine kinase (CK). Although such elevations seem to be more pronounced in patients with marked acidemia or with more severe respiratory insufficiency, a convincing correlation between disease severity and CK elevation has not been established. Though the CK-myocardial bound isoenzyme is increased in some patients, most elevations in CK are not secondary to cardiac disease. However, patients with acute severe asthma do have risk factors for acute cardiac injury, including hypoxemia, acidosis, and high myocardial energy demand. Troponin may be elevated even in patients without known cardiac disease. In one study, 36% of critical asthma patients without known cardiac disease ( n = 64) who had troponin measured as part of clinical care had elevated levels, and all eight cases of troponin greater than 0.5 ng/mL (range, 1.0–12.6 ng/mL) were associated with sustained diastolic hypotension. Diastolic hypotension develops in many children treated with continuous β-agonist medications, potentially decreasing coronary perfusion, which should be monitored.
Patients with significant airway obstruction and hyperinflation may exhibit a change in the mean frontal P-wave vector. A P-wave axis greater than 60 degrees has been associated with hyperinflation in both pediatric and adult patients with airway obstruction and is thought to represent positional atrial changes caused by inferior displacement of the diaphragm.
Twelve-lead electrocardiography (ECG) and continuous cardiac monitoring are valuable tools in the care of patients with critical asthma. These patients usually receive high doses of β-agonist drugs and may show evidence of hypokalemia (low-voltage T waves) or cardiac arrhythmias. , The already increased myocardial energy demand resulting from airway obstruction is compounded by the chronotropic and vasodilatory effects of β-agonist drugs and may lead to myocardial ischemia, particularly in adult patients with restricted coronary perfusion. Pediatric patients may exhibit ECG and enzymatic evidence of myocardial ischemia, particularly during treatment with intravenously administered isoproterenol. However, despite the fact that a study reported a high percentage (66%) of patients exhibiting nonspecific ST-segment changes or other criteria suggestive of ischemia, these changes were not well correlated with initiation of terbutaline therapy or elevations in cardiac troponin T.
Measurement of peak expiratory flow rates can be used to estimate the degree of airway obstruction and response to therapy in patients presenting to the emergency department with an acute asthma attack. This is less useful in the ICU because sick children with severe respiratory distress may be unable to perform an adequate forced expiratory maneuver. Measurements also may not be reliable in younger patients who are incapable of coordinating a rapid forced expiratory effort.
Initial management in the emergency department
Pediatric patients with mild acute asthma exacerbations generally are treated in the emergency department with one or more doses of an inhaled β-agonist, such as albuterol (salbutamol). Most of these patients also should receive a systemic corticosteroid, such as prednisone, and then can be sent home to complete a 3- to 5-day course of therapy. Patients with mild disease often respond well to initial treatment and do not require the attention of a pediatric intensivist.
Patients with moderate or severe acute asthma exacerbations require aggressive treatment from the outset. Because most patients with moderate or severe exacerbations have enough intrapulmonary shunt to result in hypoxemia, supplemental oxygen therapy should be initiated at the earliest time possible. The inspired oxygen can be adjusted once peripheral capillary oxygen saturation (Sp o 2 ) is measured with a goal above 92%. It should not be assumed that ventilation is adequate in a patient with normal Sp o 2 during the administration of supplemental oxygen therapy.
Nebulized β-agonist agents such as albuterol are the most commonly used first-line therapy in the emergency department. The usual albuterol dose ranges between 0.05 and 0.15 mg/kg, diluted with 1 or 2 mL of normal saline solution. However, from a practical standpoint, patients weighing 20 kg or more typically are administered 5-mg doses, whereas patients weighing less than 20 kg receive 2.5-mg doses. Albuterol doses are repeated every 20 minutes during the first hour, with the need for additional doses dictated by clinical response.
Patients with moderate or severe acute asthma should also receive a dose of systemic corticosteroid in the emergency department, typically prior to the second dose of albuterol. Prednisone (2 mg/kg) can be administered orally and generally is well tolerated. Oral prednisone is superior to inhaled fluticasone in children with severe asthma, as evidenced by greater improvement in pulmonary function and lower hospitalization rates. Alternatively, dexamethasone administered as a single intramuscular dose (0.3–1.7 mg/kg) or enterally (0.6 mg/kg daily for 2 days) has been shown to be equivalent to 5-day courses of prednisone with less emesis. The role of corticosteroids in reversing an acute asthma exacerbation in the emergency department has been the subject of debate, considering that these drugs require at least 4 to 6 hours for peak effects to be manifested. However, regardless of considerations about onset of action, acute suppression of inflammation is a cornerstone of acute asthma treatment, and there is evidence that early administration may reduce the rate of hospitalization. In addition, corticosteroids increase the density, affinity, and functionality of β-adrenergic receptors in both normal and catecholamine-desensitized conditions, thus increasing the efficacy of coadministered β-adrenergic agents. This mechanism may explain, at least in part, the rapid clinical improvement exhibited by some patients treated with a combination of corticosteroid and β-adrenergic agents. Patients with more severe asthma exacerbations, those unable to tolerate oral medication because of respiratory distress or emesis, or those with a history of nausea during intensive β-agonist therapy should be given parenteral corticosteroids. such as methylprednisolone (2 mg/kg administered intravenously, followed by 0.5–1 mg/kg per dose administered intravenously every 6 hours).
Inhaled or nebulized anticholinergic agents such as ipratropium bromide are a common adjunct to the treatment of asthma exacerbations in the emergency department. In patients treated with one dose of a corticosteroid, use of ipratropium bromide (500 μg/2.5 mL) in conjunction with the second and third albuterol doses has been associated with greater clinical improvement and reduced hospitalization rates compared with corticosteroid and albuterol alone.
Magnesium sulfate administered as a single intravenous bolus (25–40 mg/kg over 20 minutes) has been shown to reduce hospitalization rates in children with moderate to severe asthma when administered in the emergency department. , In practice, magnesium sulfate is more commonly used as an adjunct in severe asthma to prevent respiratory failure and ICU admission.
Most patients with an acute asthma exacerbation respond to treatment in the emergency department and are discharged home. Among patients whose symptoms persist despite initial treatment, most can be managed safely in the general pediatric inpatient ward. Indications for hospitalization after treatment in the emergency department are loosely defined but may include (1) an inadequate response to three or four aerosol treatments; (2) relapse of respiratory distress within 1 hour of receiving treatment with aerosols and steroids; (3) persistent Sp o 2 measurements of less than 91% in room air; (4) the need for oxygen therapy; (5) a significant reduction in peak expiratory flow rate, especially with a poor response to bronchodilators; (6) having unreliable family support or being unable to comply with outpatient treatment; and (7) multiple visits for the same episode. , Patients who require higher levels of monitoring, more invasive and aggressive treatment, or who deteriorate during hospitalization in the general pediatric ward should be admitted to the PICU.
Management in the intensive care unit
Patients with critical asthma who are admitted to the ICU represent a heterogeneous group, thus requiring different levels of monitoring and treatment. However, all patients who are sick enough to warrant admission to the ICU should be monitored using continuous ECG tracing, continuous respiratory rate, noninvasive blood pressures, and Sp o 2 . Sicker patients who require frequent blood sampling will benefit from an indwelling arterial catheter. Patients in respiratory failure requiring mechanical ventilation should have reliable and adequate central venous access.
Patients with more severe asthma exacerbations universally exhibit hypoxemia as a result of intrapulmonary shunts caused by mucus plugging, atelectasis, and hyperinflation. Treatment with β-agonist agents also contributes to hypoxemia by abolishing regional pulmonary hypoxic vasoconstriction and increasing intrapulmonary shunt. , Patients may have hypoxemia despite a normal-appearing chest radiograph, as regional hyperinflation may result in the conversion of lung segments from West zones 3 and 2 to zone 1, increasing ventilation-perfusion mismatch. Therefore, humidified oxygen should be used for bronchodilator nebulization and continuously between treatments. Supplemental oxygen can safely be incorporated into the treatment algorithm, because, unlike in some adult patients with severe chronic obstructive pulmonary disease or asthma, no evidence exists to suggest that supplemental oxygen suppresses the respiratory drive in children with critical asthma.
Patients with critical asthma usually present with decreased total body water because of decreased oral fluid intake and increased insensible water losses. Therefore, most patients require some degree of volume expansion. This should be carefully balanced with the need to avoid overhydration because of the propensity for transcapillary fluid migration and alveolar flooding exhibited by some patients with large swings in intrathoracic pressures, potentially resulting in worse clinical outcomes. The need for rapid fluid expansion often becomes obvious shortly after intubation of patients with low intravascular volumes who are receiving β-agonist agents. Patients should remain NPO and on isotonic intravenous fluids until an improvement in respiratory status allows for the safe initiation of enteral nutrition.
Corticosteroids play a central role in the treatment of patients with critical and near-fatal asthma, considering that these conditions are predominantly inflammatory in nature. Glucocorticosteroid agents modulate airway inflammation by a number of mechanisms, including direct interaction with cytosolic receptors and glucocorticosteroid response elements in gene promoters and indirect effects on the binding of transcription factors (such as nuclear factor–κB) and on other cell-signaling processes, such as posttranscriptional events. Gene products suppressed by glucocorticosteroid agents include a wide range of cytokines (IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-11, IL-12, IL-13, tumor necrosis factor-α, and granulocyte-macrophage colony-stimulating factor), adhesion molecules (intracellular adhesion molecule-1 and vascular cell adhesion molecule-1), and inducible enzymes, including NO synthase and cyclooxygenase-2. Transcription of other genes, such as lipocortin-1 and the β 2 -adrenergic receptor, may be enhanced. Glucocorticosteroid agents also decrease airway mucus production, reduce inflammatory cell infiltration and activation, and attenuate capillary permeability.
In children with critical or near-fatal asthma, glucocorticosteroids should be administered by the IV route. The oral route may be used in selected cases, but inhaled glucocorticosteroids play no role in the treatment of the hospitalized patient. , The most common agent used in the United States is methylprednisolone due to its wide availability as an IV preparation and lack of mineralocorticoid effects. The usual dose of methylprednisolone is 0.5 to 1 mg/kg per dose, administered IV every 6 hours. Hydrocortisone, an agent with both glucocorticoid and mineralocorticoid activity, can be used as an alternative at doses of 2 to 4 mg/kg per dose, administered IV every 6 hours. Short courses of steroids typically are well tolerated without significant adverse effects. However, hypertension, hyperglycemia, mood disorders, and serious viral infections, such as fatal varicella, have been reported in previously well patients with asthma who have received glucocorticosteroid drugs. Duration of corticosteroid therapy is dictated by the severity of illness and clinical response, but it should be noted that airway inflammation continues long after the clinical symptoms improve. Once initiated, treatment with systemic corticosteroids is continued for 5 to 7 days and followed by long-term inhaled steroids. Longer treatment courses necessitate gradual weaning of the drug to decrease the chances of symptomatic adrenal insufficiency or relapse. Prophylaxis with an H 2 blocker or proton pump inhibitor should be considered because of the possibility of steroid-associated gastritis and gastric perforation.
The β-agonist properties of the sympathomimetic agents cause bronchial smooth muscle relaxation and, hence, bronchodilation. These agents also can increase diaphragmatic contractility, enhance mucociliary clearance, and inhibit bronchospastic mediators from mast cells. Therefore β-agonists, along with systemic corticosteroids, are the mainstay of pharmacotherapy in persons with critical and near-fatal asthma. β 2 -receptor selectivity is desirable to avoid adverse effects of nonselective α- and β 1 -adrenergic receptor stimulation. However, despite relative β 2 selectivity, cardiovascular adverse effects remain a dose-limiting factor. The relative potency of various agents for the β 2 receptor is as follows: isoproterenol > fenoterol > albuterol > terbutaline > isoetharine > metaproterenol. Of these, only albuterol and terbutaline are widely used in clinical practice.
Once bound to the β-adrenergic receptor, β-agonists activate adenyl cyclase, resulting in increased intracellular cyclic adenosine monophosphate (cAMP) levels, which leads to bronchial and vascular smooth muscle relaxation. Dose-response curves demonstrate that large dose increases fail to enhance bronchodilation significantly. However, as the degree of bronchial constriction increases, the bronchodilation dose-response curve shifts to the right, indicating the need for a higher dose to achieve the desired response.
In persons with near-fatal asthma, parenteral and aerosol routes of administration are used exclusively. Traditional therapy for persons with critical asthma previously included subcutaneous doses of epinephrine, but epinephrine is no longer widely used because of the development of newer, more selective β-agonist agents with longer durations of action and fewer adverse effects.
The most frequent adverse effects of β-agonist agents are skeletal muscle tremor, nausea, and tachycardia. These adverse effects are common to nonselective and selective β 2 -agonist drugs administered either by IV or inhalational routes. Other cardiovascular adverse effects include blood pressure instability (predominantly diastolic hypotension) and cardiac dysrhythmias. , Myocardial ischemia has been well documented as a serious complication of IV (and inhalational) isoproterenol administration to children with critical asthma. , However, continuous IV infusions of terbutaline generally are safe and are not associated with significant cardiotoxicity. Prolongation of the QTc interval and hypokalemia have been observed during IV infusions of β-agonist drugs. Hypokalemia occurs even with a relatively stable total body potassium and is the result of intracellular potassium shifting resultant, at least in part, from an increased number of sodium-potassium pumps and not from augmented potassium elimination. Therefore, supraphysiologic potassium supplementation is rarely necessary. A common significant adverse effect of β-agonist agents is hypoxemia. This is related to drug-mediated pulmonary vasodilation overcoming local hypoxic vasoconstriction increasing perfusion to poorly ventilated lung units and intrapulmonary shunt. ,
Albuterol is the most β 2 -specific aerosol agent available in the United States. It usually is administered every 20 minutes during the initial phase of treatment at a dose of 0.05 to 0.15 mg/kg. The optimal dose and frequency of albuterol are variable and affected by spontaneous tidal volume, breathing pattern, device, and technique. On average, less than 1% of the nebulized drug is deposited in the lung. After the initial series of three albuterol treatments, continuous albuterol nebulization should be started for patients who require nebulization treatments more frequently than every hour.
Continuous albuterol nebulization appears to be superior to repeated intermittent dosing and does not cause significant cardiotoxicity. A small prospective, randomized study in children with critical asthma and impending respiratory failure indicated that children treated with continuous albuterol nebulization had more rapid clinical improvement and shorter hospitalizations than children treated with intermittent albuterol doses. Continuous administration of albuterol also was associated with more efficient allocation of respiratory therapists’ time and could offer the added advantage of more hours of uninterrupted sleep to patients. The usual dose of continuously administered albuterol ranges between 0.15 and 0.45 mg/kg/h, with a maximum dose of 20 mg/h. Higher doses of albuterol have been used in patients who are unresponsive to standard treatment. However, we do not support this practice, because the intensification of adverse effects usually outweighs any small incremental gain in bronchodilatory effect. It should be remembered that a major component of bronchial obstruction in severe asthma is from airway wall edema and mucus obstruction of the airways, neither of which is responsive to bronchodilators.
Albuterol is a 50:50 mixture of R-albuterol (levalbuterol), the active enantiomer that causes bronchodilation, and S-albuterol, which was thought to be inactive in humans. Levalbuterol, the pure R-isomer, is approved for use in the United States as a preservative-free nebulizer solution. The purported advantage of levalbuterol over albuterol stems from the fact that S-albuterol may not be completely inert and has a longer elimination half-life than R-albuterol. , However, the notion that S-albuterol is not inert and that it is capable of clinically significant adverse effects is not universally accepted. A large randomized controlled trial of levalbuterol versus racemic albuterol in children with asthma demonstrated a decreased rate of hospitalization in patients treated with levalbuterol. However, this study had methodological problems, as the primary outcome variable (rate of hospital admission) was left to the discretion of the treating physicians, and none of the secondary outcome variables were significantly different between treatment groups once the patients had been admitted to the hospital. More recent randomized clinical studies in children with asthma failed to show that levalbuterol is superior to racemic albuterol. The notion that levalbuterol causes less tachycardia than racemic albuterol has also been disproven. Furthermore, although the cost of levalbuterol has decreased significantly in the past few years, this drug continues to be more expensive than albuterol (M.L. Biros, PharmD, Rainbow Babies & Children’s Hospital, personal communication, 2019). Considering the lower cost of albuterol and the lack of clinical evidence supporting the superiority of levalbuterol, we favor albuterol as the routine bronchodilator of choice in children with critical and near-fatal asthma.
Intravenously administered albuterol is not available in the United States. However, the efficacy of albuterol infusions in patients with severe asthma has been well established in countries where the IV preparation is available. ,
Terbutaline is a relatively selective β 2 -agonist with a mechanism of action similar to albuterol. It is the most commonly used parenteral β-agonist in the United States and is available for nebulization, subcutaneous injection, and IV administration. Because of its lower β 1 -receptor affinity, subcutaneous administration of terbutaline has largely supplanted the use of epinephrine in patients with severe acute asthma. Subcutaneous terbutaline is very rarely used in the PICU; it is reserved for patients with acute worsening of respiratory status who do not have vascular access and in whom access cannot be easily obtained. Subcutaneous terbutaline is more commonly used in the management of sick patients in the emergency department and before hospital contact. The usual subcutaneous terbutaline dose is 0.01 mg/kg per dose (maximum 0.25 mg) subcutaneously every 20 minutes for three doses, as necessary.
Terbutaline is commonly and safely used in the PICU by IV infusion. This therapy is indicated for patients with critical asthma who fail to improve or who show signs of deterioration during treatment with nebulized β 2 -agonists, ipratropium bromide, and steroids. The usual range of IV terbutaline dosage is 0.1 to 10 μg/kg per minute, as a continuous infusion prepared in 0.9% normal saline solution or D 5 W. In our clinical experience, however, most patients are started on a dose of 1 μg/kg per minute, and the dose is titrated to effect, with doses higher than 4 μg/kg per minute rarely necessary. Patients starting therapy at doses lower than 1 μg/kg per minute can be given a loading dose of 10 μg/kg over 10 minutes to accelerate the onset of action.
Anticholinergic agents have become an important part of the treatment of children with severe acute asthma. The typical anticholinergic agent used in treating patients with asthma is ipratropium bromide, a quaternary ammonium compound formed by the introduction of an isopropyl group to the N atom of atropine. Unlike atropine (a tertiary ammonium compound), ipratropium bromide does not cross the blood-brain barrier and does not cause central anticholinergic adverse effects. Considering that parasympathetic input influences bronchial smooth muscle tone, ipratropium bromide can produce bronchodilation by inhibition of cholinergic-mediated bronchospasm. An important property of ipratropium bromide is the lack of negative effect on ciliary bronchial epithelium, unlike the marked inhibition of ciliary beating and mucociliary clearance produced by atropine.
Nebulized ipratropium bromide (250- to 500-μg doses) can be used every 20 minutes during the first hour in the emergency department. The recommended dose for continuation therapy is 250 to 500 μg every 6 hours. After inhalation, peak responses usually develop over 30 to 90 minutes, and clinical effects may persist for more than 4 hours. Systemic effects are minimal because less than 1% of an inhaled dose of ipratropium bromide is absorbed into the circulation. However, extrapulmonary effects, such as mydriasis and blurred vision, have been reported from inadvertent topical ocular absorption of the drug. ,
The addition of ipratropium bromide to nebulized albuterol in the treatment of bronchospasm makes pharmacologic sense because albuterol causes bronchodilation by increasing cAMP levels, while the effect of ipratropium bromide is mediated by a decrease in cyclic guanosine monophosphate. The combined use of ipratropium bromide and nebulized albuterol to treat children with asthma who present to the emergency department has proved to be cost effective.
Magnesium is a physiologic calcium antagonist that inhibits calcium uptake and relaxes bronchial smooth muscle. It has been known for more than 60 years that magnesium causes bronchorelaxation in patients with asthma, but its use as an adjunct in treating patients with severe asthma has occurred only recently. Numerous reports, case series, and randomized controlled trials have suggested clinical improvement when asthmatic patients receive IV magnesium sulfate infusions in the emergency department or ICU. , While there is some evidence that magnesium is as effective as albuterol when delivered by nebulization and has been used successfully as a liquid vehicle for albuterol nebulization, a larger trial failed to show a significant benefit on hospital length of stay.
The indication for IV magnesium sulfate in children with critical or near-fatal asthma is still unclear because of the paucity of randomized controlled trials. Some studies suggest that magnesium sulfate infusions are associated with significant improvements in short-term pulmonary function. Another study failed to show improvement in disease severity or a reduction in hospitalization rates. More recent studies indicate an association between magnesium sulfate use and longer durations of continuous albuterol and hospital length of stay but may be related to preferential use of magnesium in patients with more severe disease. , The usual dose of magnesium sulfate in children with critical or near-fatal asthma is 25 to 40 mg/kg per dose, infused intravenously, over 20 to 30 minutes. The onset of clinical response is rapid (occurring in minutes) and generally is observed during the initial infusion. Patients should be carefully monitored for adverse effects during the infusion, which include hypotension, nausea, and flushing. Serious toxicity—such as cardiac arrhythmias, muscle weakness, areflexia, and respiratory depression—is not a significant concern with the use of magnesium sulfate in persons with acute asthma when used as directed. The IV infusion of magnesium sulfate under controlled conditions is safe; a subset of patients with critical and near-fatal asthma clearly responds to this therapy, which may reduce the need for mechanical ventilator support. , , A systematic review of published randomized controlled trials supports the use of magnesium sulfate in addition to β 2 -agonist agents and systemic steroid drugs in the treatment of persons with acute severe asthma.
Methylxanthine agents, as the name implies, are substances formed by the methylation of xanthine, and include caffeine, theobromine, and theophylline. The water solubility of methylxanthine agents is very low but can be greatly enhanced by the formation of complexes with a variety of compounds. Most notably, the combination of theophylline and ethylenediamine yields aminophylline, a water-soluble salt.
The exact molecular mechanism of theophylline-mediated bronchodilation is unclear but is thought to involve its action as a phosphodiesterase-4 inhibitor, reducing the degradation of cAMP. This in turn mediates cellular responses that result in bronchial smooth muscle relaxation. Other mechanisms of action have been proposed, including inhibition of phosphoinositide 3-kinase activity, adenosine receptor antagonism, increasing histone deacetylase activity, stimulation of endogenous catecholamine release, prostaglandin antagonism, and alterations in intracellular calcium mobilization. Theophylline is also known to cause inhibition of afferent neuronal activity, leading to inhibition of bronchospasm mediated by reflex activation of cholinergic pathways. Theophylline has antiinflammatory and immunomodulatory actions and is known to augment diaphragmatic contractility and increase respiratory drive.
In isolated human bronchial preparations, in vitro theophylline concentrations greater than 70 μmol/L can induce a 50% reversal of bronchoconstriction. Such high local concentrations presumably would be achieved with plasma levels greater than 10 to 20 μg/mL. In clinical practice, however, this range poses a difficult problem because of the narrow window between therapeutic levels and toxicity, which often overlap. The half-life of theophylline ranges from 3 to 7 hours. Therefore, aminophylline, which is equivalent to 80% theophylline, generally is administered as a continuous IV infusion to avoid significant fluctuations in serum concentrations. Typically, a loading dose is given to achieve serum levels between 10 and 20 μg/mL. Assuming a normal average volume of distribution, a 1 mg/kg dose of theophylline (1.25 mg/kg of aminophylline) raises the serum concentration by 2 μg/mL. The loading dose should be administered over 20 minutes and should be followed immediately by the continuous infusion of the drug. Empiric doses of aminophylline can be started for patients with normal hepatic and cardiac function as follows: infants younger than 6 months, 0.5 mg/kg per hour; infants aged 6 months to 1 year, 0.85 to 1 mg/kg per hour; children aged 1 to 9 years, 1 mg/kg per hour; and children older than 9 years, 0.75 mg/kg per hour. Patients with compromised hepatic or cardiovascular function should be started at a dose of 0.25 mg/kg per hour. Obese patients should have doses calculated on ideal body weight to prevent toxicity. Serum drug levels should be monitored 30 to 60 minutes after the loading dose and frequently during the continuous infusion, considering that steady-state concentrations are not achieved until approximately five half-lives, which corresponds to 24 to 36 hours of infusion.
A number of studies in adults and children with acute asthma indicate that therapy with theophylline or aminophylline is of no clinical benefit. Randomized, placebo-controlled trials have tested the efficacy of aminophylline and theophylline in children with critical asthma. Aminophylline treatment resulted in improved physiologic outcomes, such as oxygenation and pulmonary function testing, but did not decrease ICU length of stay and was associated with adverse effects, such as nausea and vomiting. Theophylline was associated with faster clinical improvement, but it had no effect on PICU length of stay and led to a significantly higher frequency of vomiting compared with control subjects.
Use of these agents has decreased significantly considering the narrow therapeutic window (10–20 μg/mL) that often overlaps the toxicity (>15 μg/mL); the questionable evidence of clinical efficacy; and that methylxanthine agents have been associated with adverse effects ranging from nausea, vomiting, and fever to dyskinesias, seizures, and death. In fact, methylxanthines were used in less than 6% of children with critical and near-fatal asthma admitted to PICUs in a multicenter study in the United States. With these considerations in mind, we consider using methylxanthine agents only in occasional selected patients who fail to respond to maximal therapy with β-agonist agents, steroids, anticholinergic drugs, magnesium sulfate, and other adjuncts.
Helium is a biologically inert gas that is less dense than any gas except hydrogen and is about one-seventh as dense as air. The medicinal application of helium and oxygen mixtures (heliox) in the treatment of asthma and extrathoracic airway obstruction has been known for over 8 decades. Because of its low density, heliox reduces the Reynolds number. This effect is associated with a reduced likelihood of turbulent gas flow while facilitating laminar gas flow in the airways, thus decreasing the work of breathing in situations associated with high airway resistance. Heliox provides a theoretical benefit in patients with obstructive lesions of the extrathoracic and intrathoracic airways. Several reports advocate the benefit of heliox in the management of children with extrathoracic airway obstruction. , The role of heliox in patients with asthma is less clear.
Research using heliox mixtures has demonstrated a greater percentage of lung particle retention and greater delivery of albuterol from both metered-dose inhalers and nebulizers, , suggesting that one of the beneficial effects of heliox use in patients with asthma is improved deposition of aerosolized drugs. While there is some evidence that 70%/30% heliox-driven continuous nebulized albuterol treatments are associated with a greater degree of clinical improvement compared with oxygen-driven continuous nebulized albuterol in children with moderate to severe asthma exacerbations, other studies have shown no significant improvement in hospital or ICU length of stay. The higher the needed fractional inspired oxygen concentration, the less effective the heliox mixture.
Heliox has been recommended by some investigators as a useful adjunct in adult patients with severe asthma, both during spontaneous breathing and mechanical ventilation. Anecdotal reports suggest that heliox is associated with improvement in pulmonary function in children with acute asthma. , However, a small randomized crossover trial of heliox in spontaneously breathing patients with severe asthma failed to show improvement in pulmonary function or dyspnea scores. Additionally, a systematic review of seven prospective, controlled trials in children and adults did not support the use of heliox in patients with moderate or severe acute asthma. The paucity of well-executed randomized controlled studies makes it impossible to assess the therapeutic effect of heliox in children with asthma. In addition, should heliox be beneficial in some patients, the duration of administration and optimal helium-oxygen mixture remain undetermined. Until better evidence emerges, heliox remains an unproved therapy for pediatric asthma. Its use should be restricted to individual attempts in selected patients with severe refractory critical or near-fatal asthma who do not respond to conventional treatment. To get the full benefit from the lower gas density, 80:20 or 70:30 helium-oxygen mixtures must be used, limiting the therapy to those with low inspired oxygen needs.
Ketamine hydrochloride is a dissociative anesthetic agent with bronchodilatory properties that is available in a solution for IV or intramuscular administration. After IV administration, a sensation of dissociation is generally experienced within 15 seconds, followed by unconsciousness after another 30 seconds. This reaction is followed by profound analgesia that lasts 40 to 60 minutes and amnesia that may persist for 2 hours. Some patients, particularly older children, may experience a postanesthesia emergence reaction with confusion, agitation, and hallucinations. Usual ketamine doses do not significantly affect hypoxic or hypercarbic respiratory drive. Pharyngeal and laryngeal reflexes are maintained and, although the cough reflex is somewhat depressed, airway obstruction does not normally occur. Aside from its anesthetic properties, ketamine causes sialorrhea and increases airway secretions, cardiac output, heart rate, blood pressure, metabolic rate, cerebral blood flow, and intracranial pressure. Pulmonary vascular resistance is not altered, and hypoxic pulmonary vasoconstriction is preserved. Ketamine inhibits bronchospasm and lowers airway resistance, presumably through blockage of N -methyl- d -aspartate receptors in airway smooth muscle. The bronchodilatory effect of ketamine makes it an attractive agent in patients with asthma who require sedation and anesthesia for intubation or mechanical ventilation. , However, the bronchodilatory effects of ketamine may be counteracted by the observed increase in airway secretions and sialorrhea.
Questions exist regarding the use of ketamine in nonintubated patients with critical asthma. In the emergency department, ketamine infusion added to standard therapy of nonintubated patients has not shown a clinical benefit. However, limited evidence suggests that this therapy may be helpful in selected patients when trying to avoid the need for mechanical ventilation. In our experience, the administration of ketamine to nonintubated children with critical asthma frequently precedes the need to intubate and is rarely associated with significant and noticeable clinical improvement. For this reason, attempts at administering ketamine to nonintubated children with severe critical asthma should always take place in the ICU under strictly monitored conditions and with personnel capable of rapidly establishing an airway for initiation of ventilatory support.
Ketamine usually is administered as an IV bolus of 2 mg/kg, followed by a continuous infusion of 1 to 2 mg/kg per hour. The resulting sialorrhea and increased airway secretions can be attenuated by administration of glycopyrrolate or atropine. The concurrent use of benzodiazepines may attenuate the agitation and hallucinations in patients who experience emergence reactions following ketamine anesthesia.
Only a small minority of patients with near-fatal asthma admitted to the PICU (10%–12%) require endotracheal intubation and mechanical ventilation. The indications for intubation are not precisely defined; the decision to proceed with intubation is based largely on clinical judgment. Absolute indications are obvious and include cardiac or respiratory arrest, profound hypoxemia refractory to supplemental oxygen administration, and respiratory failure. The decision to intubate should not be based solely on blood gas results. However, the presence of a mixed respiratory and metabolic acidosis, persistent hypoxemia, and agitation or obtundation, despite maximal therapeutic efforts, indicate impending respiratory arrest and signal the urgent need to proceed with intubation and mechanical ventilation.
Some patients with critical asthma will benefit from attempts to attenuate respiratory muscle fatigue through a trial of noninvasive ventilation. , Noninvasive bilevel positive airway pressure should be employed so that the set inspiratory positive airway pressure (iPAP) assists the patient in overcoming the increased airway resistance and respiratory muscle fatigue, while the set expiratory positive airway pressure (ePAP) helps offset the intrinsic positive end-expiratory pressure (PEEP) and aids trigger synchrony. We generally initiate noninvasive ventilation in spontaneous mode without a backup rate, with an iPAP of 10 cm H 2 O and an ePAP of 5 cm H 2 O. The iPAP can be titrated up based on the degree of inspiratory work of breathing and to generate a desired tidal volume of 6 to 9 mL/kg. The ePAP may also be increased for improved synchrony and comfort, but levels greater than 8 cm H 2 O are rarely indicated and may contribute to hyperinflation. The use of bilevel positive airway pressure requires patient cooperation and a well-sealed mask, which may prove difficult in an anxious and agitated child with impending respiratory failure. However, this should not preclude a trial of noninvasive ventilation, as many responders experience rapid improvement of respiratory distress and dyspnea, with attendant decrease in agitation. ,
The intubation of patients with near – fatal asthma is complicated by the fact that these patients are, by definition, fatigued, acidotic, and often also hypoxemic or agitated. Once the decision to intubate is reached, the procedure should be performed promptly by a skilled operator with experience in rapid sequence intubation. Intubation should be preceded by the administration of an anesthetic, such as an opiate, propofol, or ketamine; a benzodiazepine; and a neuromuscular blocker. Ketamine is the preferred anesthetic because of its properties as a bronchodilator. Among the opiates, fentanyl is a widely available choice; morphine should be avoided because it is associated with histamine release and could, at least in theory, contribute to the allergic and inflammatory process. A rapid – acting neuromuscular blocker such as succinylcholine can be used to induce chemical paralysis. More commonly, a nondepolarizing neuromuscular blocker is used, such as vecuronium, rocuronium, or cisatracurium. The patient should be preoxygenated with 100% oxygen by face mask during spontaneous breathing. Assisted breathing with a bag – mask apparatus can be performed with care taken to avoid worsening of dynamic hyperinflation and gastric distension. Whenever possible, a nasogastric tube should be placed in advance to decompress the stomach.
A cuffed endotracheal tube should be introduced and its placement confirmed by a colorimetric method or capnography, auscultation, and chest radiograph. Special attention to the manual ventilation technique is needed to avoid fast rates that often are inadvertently applied immediately following intubation. Rapid respiratory rates applied to intubated children with severe airway obstruction lead to iatrogenic hyperinflation, hypoxemia, and hemodynamic instability (hypotension). These patients require slow respiratory rates with very prolonged expiratory times to allow for adequate gas exchange and lung volumes. A helpful technique is to use a stethoscope to auscultate for the disappearance of expiratory wheezes prior to starting the next inspiration. The occurrence of oxygen desaturation and hypotension following intubation should prompt an equipment check and confirmation of tube placement. A tension pneumothorax must be considered in patients with hypoxemia and hypotension who fail to improve rapidly after administration of fluids and optimization of ventilation (or brief endotracheal tube disconnection), particularly when unequal breath sounds are present.
The goal of mechanical ventilation in patients with near-fatal asthma is to reverse hypoxemia (if present), relieve respiratory muscle fatigue, and maintain a level of alveolar ventilation compatible with an acceptable pH, while avoiding iatrogenic hyperinflation and levels of intrathoracic pressure that reduce cardiac output. Ill-advised attempts to achieve a normal Pa co 2 would require fast respiratory rates, high minute volumes, and very high airway pressures, all of which are associated with the development of air leak (pneumothorax and pneumomediastinum) and high mortality rates.
A paradigm shift in the ventilatory management of patients with asthma occurred with the introduction of a strategy of controlled hypoventilation reported by Darioli and Perret. Their strategy resulted in no mortality in 34 episodes of mechanical ventilation in 26 patients and significantly lower complication rates in comparison with historical controls. This approach used tidal volumes between 8 and 12 mL/kg and targeted peak airway pressures up to 50 cm H 2 O. Tidal volumes were reduced if the peak pressure limit could not be respected and higher Paco 2 measurements were tolerated. A similar approach using respiratory rates lower than 12 breaths/min, tidal volumes between 8 and 12 mL/kg, peak inspiratory pressures of 40 to 45 cm H 2 O, and permissive hypercapnia also resulted in very few complications and no mortality or long-term morbidity in 19 mechanically ventilated children with near-fatal asthma.
The modes of ventilatory support for patients with severe acute asthma can be divided between pressure and volume preset. No definitive evidence exists to suggest that one mode of ventilation is superior to the other. However, to safely ventilate a patient with asthma, the characteristics of each mode must be fully understood. Pressure control modes use a decelerating gas flow and have the advantage of ensuring that a particular inspiratory pressure limit is respected. The main disadvantage of pressure control modes is that tidal volumes can vary greatly with changes in airway resistance and respiratory compliance. Volume control modes deliver a constant tidal volume provided that there is no significant air leak around the endotracheal tube. An added advantage of volume control is that it allows for comparison of peak inspiratory pressure and plateau pressure measurements (peak-to-plateau pressure), which can serve as a longitudinal indicator of airway resistance and response to therapy. For these measurements, the plateau pressure is obtained by performing an inspiratory hold and is then compared with the peak inspiratory pressure ( Fig. 50.3 ). Increasing peak-to-plateau pressure indicates increasing airway resistance, whereas decreasing peak-to-plateau pressure suggests a response to therapy. A disadvantage of volume control ventilation is that very high lung volumes can develop if exhalation is incomplete because tidal volumes remain constant breath to breath. The option of using pressure-regulated volume control, a mode available on several ventilators, offers many of the combined advantages of pressure control and of volume control, including optimal decelerating inspiratory gas flow, assured tidal volumes, and minimized airway pressures.