STATUS ASTHMATICUS S. Agarwal, MD, S. Kache, MD Definition Status asthmaticus is a life-threatening form of asthma in which progressively worsening reactive airways are unresponsive to usual appropriate therapy that leads to pulmonary insufficiency. Epidemiology In 1994, the prevalence of status asthmaticus was 7.4% in children ages 5-14 years old with asthma. The rate of death was noted to be 3.7 per 1 million children aged 5-14 years in 1995. The risk factors for death in adults include: Male gender Presentation with severe mixed acidosis with extreme hypercapnia (pco2= 97+/- 31) Silent chest exam on admission The risk factors for death in children include: Requiring intubation Prior admission to intensive care unit for asthma Chronic use of oral corticosteroids More than 2 hospitalizations for asthma in the past year, more than 3 Emergency visits to the hospital or health professional s office in the past year History of non-compliance History of family disturbances Living in poverty Underestimating severity of acute attack (American Academy of Allergy, Asthma, and Immunology (2000). Allergy Report). Pathophysiology Status asthmaticus is a reversible, recurrent, diffuse obstructive pulmonary disease process caused by airway inflammation and hyper-reactivity. The primary pathophysiology includes: Smooth muscle spasm Mucosal edema Mucous plugging. These changes in the airway cause airflow obstruction leading to premature airway closure on expiration which causes hypercarbia and dynamic hyperinflation. This dynamic hyperinflation or air-trapping also leads to ventilation / perfusion (V/Q) mismatching causing hypoxemia. Clinical Presentation The primary signs & symptoms of asthma are cough, dyspnea, and wheezing. SA patients may be unresponsive to treatment, have minimal respiratory reserve and have a deteriorating clinical condition. Upper respiratory tract infections are often found concomitantly and exacerbate the acute reactive airway process. The Status Asthmaticus 1
presence or absence of wheezing while examining a child with SA requires special attention. The clinical exam of wheezing changes as the disease progresses: - Expiratory wheeze: airways only obstruct during expiration Disease Progression - Inspiratory and expiratory wheeze: airways are obstructed throughout the respiratory cycle - Little air movement heard ( tight ): complete airway obstruction occurs despite maximal patient effort suggesting impending respiratory failure Other exam findings that signify severe respiratory function compromise include: Retractions Prolonged expiratory phase Pulsus paradoxus - systolic blood pressure drop of more than 18 mmhg with inspiration in teenagers or more than 10 mmhg in children Evidence of cyanosis/hypoxemia - PaO 2 less than 60mmHg, change in consciousness Hypercapnia - PaCO 2 greater than 40mmHg in presence of dyspnea and wheezing Metabolic acidosis FEV1 or PEFR (peak expiratory flow rate) less than 20% predicted with little or no response to acute therapy Differential Diagnosis The differential for wheezing in the pediatric population is extensive and should be considered in a patient presenting with wheezing for the first time. Some of the more common diagnoses include laryngotracheomalacia, other congenital malformations, vocal cord dysfunction, foreign body, infection (croup, bronchiolitis, pneumonia), and cardiac disease. Not all wheezing is asthma. Diagnostics A chest radiograph should be obtained to define the extent of the associated parenchymal disease and to rule out other diagnoses (e.g. foreign body, infiltrate). Hyperinflation and peribronchial thickening are common findings. Laboratory tests to evaluate the degree of acidosis and for a potential infection are beneficial. Spirometry can be useful to also assess severity of disease. A fall in FEV1 has been shown to correlate well with the degree of airway obstruction and hypoxemia in status asthmaticus. Blood gases: Although, blood gases are often discussed in asthma management, they should not be used to determine the need for intubation. The patient s clinical status should be the grounds for intubation see intubation section below. An attempt at a blood gas often only agitates the patient further exacerbating the reactive airway process. Therefore, the need for a blood gas should be determined prior to acquiring one. Status Asthmaticus 2
General Principles of Management 1. An initial drop in O 2 saturation may occur once treatment is initiated. After the initial bronchospasm, as the disease progresses, hypoxic vasoconstriction causes shunting of blood away from poorly ventilated lungs. With treatment, the vascular smooth muscle presumably dilates first causing intra-pulmonary shunting and a transient desaturation. This drop in O 2 saturation quickly resolves and bronchial constriction improves. 2. If it is necessary to assist a patient with status asthmaticus with positive pressure ventilation (bag-valve-mask or ventilator), use the slowest rate required to maintain appropriate oxygenation allowing for a long expiratory time. It must be recognized that intubation is not a treatment for asthma, but merely temporizes the respiratory failure as other treatments take effect and the inflammatory process resolves. 3. Declining oxygen saturations is a marker of impending respiratory failure. Normal O2 saturations however do not indicate adequate respiratory reserve. Treatment Intravenous Fluids: Patients in SA are inevitably dehydrated due to poor oral intake, tachypnea, and often emesis. The dehydration often causes a metabolic acidosis as well increasing their work of breathing. Rehydration prevents thickening of mucous secretions and begins to treat the metabolic acidosis. Albuterol: first line therapy Mechanism of action: a β2 agonist responsible for smooth muscle relaxation Dosing: Continuous nebulization - 10-20 mg/hr (or 0.5-0.6 mg/kg/hour) with an oxygen flow rate of 10 12L/min Advantages: rapid acting and can be rapidly administered Disadvantages: tachycardia, hyperglycemia, hypokalemia. Other: Nebulization is preferred to MDI Ipratropium bromide (Atrovent): Mechanism of action: anticholinergic, muscarinic M1, receptors mediate bronchoconstriction Dosing: 0.25 0.5 mg nebulized o Q20 min X 3 doses with continuous albuterol has proven effective in acute management o Every 6-8 hrs with Albuterol for chronic treatment Advantages: has no systemic anticholinergic action Other: unilateral pupillary dilation can occur with local med entry Corticosteroids Solu-medrol Mechanism of action: effective in controlling or preventing the sustained inflammatory phase which occurs 6-8 hours after allergen exposure Dosing: Methyl-prednisone Status Asthmaticus 3
o Loading dose: 2 mg/kg IV o Maintenance dose: 0.5mg/kg IV q 6hr Other: Steroids should be administered IV to SA patients to assure adequate drug delivery in a timely manner. Given the risk of emesis and differential absorption enterally, the drug should not be administered orally. Magnesium Sulfate Mechanism of action: smooth muscle relaxant Dosing: 50 mg/kg IV over 20 min with max of 2 gm Advantages: has been shown to be effective in severe (FEV1<25% predicted) asthma Disadvantages / Side effects: rarely noted; hypotension, respiratory depression & muscle weakness can be treated with IV Calcium Gluconate Other: respiratory depression & muscle weakness are noted only at levels >12mg/dL. Normal Mg levels are 1.5-2mg/dL and minimal increase in level is noted with a single dose of magnesium. Therefore, there should be little concern by the practitioner of causing respiratory depression with a single dose of magnesium sulfate. Terbutaline Mechanism of action: IV β2 agonist Dosing: o Loading dose: 5-10mcg/kg IV over 10 min o Continuous infusion: 0.4-4 mcg/kg/min IV Advantages: effectively reaches areas of lung by intravenous infusion that Albuterol does not due to airway obstruction Disadvantages / side effects: tachycardia, hyperglycemia, hypokalemia, (rhabdomyolysis & cardiac ischemia rarely) Other: the continuous infusion can be increased every 20-30 minutes by 0.4mcg/kg/min until the patient s symptoms begin to subside. Aminophylline Mechanism of action: phosphodiesterase inhibitor which allows for smooth muscle relaxation and augments mucociliary clearance Dosing: o Loading dose: 6 mg/kg over 20 min IV o Continuous infusion: 0.6-1 mg/kg/min IV Advantages: may prove very effective in patients resistant to above treatments given the different mechanism of action Disadvantages / side effects: nausea, vomiting, agitation, arrhythmias, seizures Other: A theophylline level needs to be checked 8 hours after drug initiation and then every morning. Therapeutic levels are 10 20 mcg/ml. Beginning a new medication should prompt a recheck of the level since multiple drugs may affect the level. Status Asthmaticus 4
Heliox Mechanism of action: It is a low-density gas that increases laminar flow and decreases turbulent flow. can be used concomitantly with Albuterol (may improve delivery), and may be given in intubated or non-intubated patients. Dosing: only effective with 60% or greater helium. Patients requiring greater than 40% FiO 2 cannot be placed on heliox. Advantages: has no systemic side effects (except causing high pitched voice) Other: The data to date is not conclusive, but small studies have shown both objective and subjective improvements in patients receiving heliox along with the prevention of intubation. In intubated patients, heliox has been shown to decrease the PIP requirements. Ketamine Mechanism of action: a dissociative anesthetic that bronchodilates by intrinsic catecholamine release, decreases airway resistance, and maintains laryngeal tone & reflexes Dosing: 0.5-1 mg/kg IV, 1 time doses Advantages: Ketamine should be the drug of choice for induction should a patient with SA requires intubation (see Chapter 11 Airway Management). Along with providing sedation for intubation, it also treats the underlying reactive airway disease Disadvantages: increases intracranial pressure Other: it can be considered in SA patients with severe agitation, but be prepared to intubate the patient should it cause hypoxia. Be cautious of agitation however since it often precedes respiratory failure. Mechanical Ventilation The two primary indications to intubate an SA patient are: Severe hypoxia Depressed level of consciousness Other potential indications for mechanical ventilation include: Obvious life-threatening respiratory distress not responding to bronchodilator therapy impending respiratory failure Hemodynamic compromise, including bradycardia, severe pulsus paradoxus Lactic acidosis associated with increased work of breathing Apnea or near-apnea Peak flows <40% of predicted The decision to intubate a patient with asthma should not be taken lightly since: 1) patients are at risk for severe decompensation during intubation 2) mechanical ventilation doesn t directly help with expiration (which is the primary problem in a patient with status asthmaticus) Status Asthmaticus 5
Potential complications include: Pneumothorax / tension pneumothorax introduction of positive pressure into hyper-inflated lungs, i.e. air-trapping Hemodynamic instability since they are often volume depleted Induction meds: Anesthetics: Ketamine (for reasons discussed above) & midazolam Paralytics: Rocuronium or another rapid onset paralytic (carry out as rapid sequence intubation) Other: Volume to prevent any hemodynamic instability; Lidocaine & Atropine to prevent any bronchospasm that maybe associated with laryngoscopy General guidelines for mechanical ventilation management: 1. Start with low tidal volume, permissive hypercapnia strategy. Tidal volume 4-7 ml/kg (prevents barotrauma / volutrauma, minimize lung distension) Low Ventilatory rate 10-14 breaths per minute I:E ratio 1:4 to 1:6 (avoid air trapping by allowing for complete exhalation) Tolerate hypercapnia Goal ph>7.25 (may require HCO 3 ) Peak pressures <30-35 2. Keep well sedated consider ketamine and versed infusions. 3. Prevent bronchoconstriction with suctioning by providing adequate sedation and Lidocaine. 4. As the patient is on steroids, limit use of paralytics (to avoid myopathy) 5. Bronchoscopy- Maybe effective in patients with signs of large mucus plugs, e.g. lobar atelectasis in CXR. Particularly seen in African-American, heavy set adolescent patients. Status Asthmaticus 6