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Status Asthmaticus


  • Status asthmaticus definition varies widely
    • Asthma attack that does not respond to initial bronchodilatory therapy and requires admission to the hospital for continued treatment
    • Severe asthma that leads to respiratory failure and need for mechanical ventilation
  • Sudden asphyxial asthma: acute dramatic onset of bronchospasm and symptoms which can quickly lead to asphyxia, cardiopulmonary arrest, and death in patients with otherwise only mild or no significant history of asthma
  • High risk patients: history of ICU admissions, history of mechanical ventilation, seizures or syncope, PaCO2 >45 mmHg, more severe baseline history of asthma.
  • African Americans 4.1 times more likely to require treatment in the ED for asthma, 2 times more likely to be hospitalized, and 7.6 times more likely to die compared with Caucasians
  • Intubation/mechanical ventilation rates for patients with asthma in the ICU vary by ICU (~2-10%)


Figure 1: Airway Changes with Asthma

  • Inflammation: marked by mast cell degranulation with accumulation of eosinophils and Th2 lymphocytes generally in response to some antigen or topical insult
  • IL-4, IL-5, IL-8, IL-13 primarily mediate inflammation, amplified by increased production of IgE by B cells
  • Airway Hyperresponsiveness: Bronchospasm due to smooth muscle activation with subsequent airflow obstruction with subsequent smooth muscle hypertrophy and hyperplasia
  • Hypersecretion of mucus: mucus plugging further impairing airflow
  • Desquamation of airways: further plugging, exposure of nerve endings leading to hyperirritable airways
  • Sometimes asthma has been referred to as: CDEB: Chronic Desquamating Eosinophillic Bronchitis
  • Triggers include: inhaled irritants like cigarette smoke or air pollution, respiratory tract infections, stress, exercise, cold air, etc. 
  • Obstruction to expiratory air flow leads to aveolar hyperinflation with resultant dead space ventilation (West Zone 1 Lung)
  • Respiratory rate increases in response to impaired ventilation; however, due to prolonged expiratory times, patients can have dynamic hyperinflation and air trapping
    • Tidal breathing at less compliant part of respiratory pressure volume curve
    • Diaphragm flattened --> Decreased generation of force
    • Increased Dead Space--> Need increased minute ventilation for adequate ventilation
    • Silent chest due to impairment in both inspiratory and expiratory flow as a result of dynamic hyperinflation
    • Elevated PVR due to increased lung volumes and sometimes hypoxia and acidosis. Furthermore, patients may be dehydrated from tachypnea and decreased oral intake. All of these work to impair VQ matching with decreased Q. Hence, fluid therapy in asthmatic patients may actually help with VQ matching, ventilation, and oxygenation.             
  • Mucus plugging results in VQ mismatch that can lead to areas of atelectasis and intrapulmonary shunting with resulting hypoxemia
  • Pulsus paradoxusDecreased arterial systolic blood pressure with inspiration (normal <10 mmHg) but with asthma, tamponade, or other conditions, can get much larger drop in SBP with inspiration
    • Various explanations but overall: with inspiration, especially forceful as with asthma, there is a large negative intrathoracic pressure. 
      1. Large negative intrathoracic pressure leads to an increase in afterload of the LV and thus decreased systolic blood pressure. 
      2. An increase in preload to the RV (bowing the septum toward the LV and thereby reducing LV preload and thus SBP- this is unlikely given RV vs LV pressures)
      3. Increased compliance of pulmonary vasculature, leading to diminished preload to the LV

Clinical Presentation

  • Respiratory distress: upright, dyspneic, short phrases
  • Rapid shallow breathing with use of accessory muscles
  • Cyanosis, gasping, exhaustion, decreased consciousness
  • Inspiratory and expiratory wheezes or worse off, the silent chest
  • Mild hypoxemia
  • Blood gas: A patient who is tachypneic and breathing hard should have hypocapnea and a mild respiratory alkalosis. A "normal" blood gas in a struggling asthmatic is very abnormal and an indication of potential impending respiratory failure
  • Peak expiratory flow: >70% of predicted used for discharge from urgent care or ED, 40-69% of predicted for continued ED or hospital treatment, <40% of predicted for care with adjunct therapies, <25% life threatening
  • Albuterol can sometimes cause transient hypoxemia when first initiated as if systemically absorbed, the Beta 2 effects also include pulmonary vasodilation, thereby countering the normal protective hypoxic pulmonary vasoconstriction that occurs, thereby leading to increased intrapulmonary shunt and hypoxemia. This is particularly the case if there is significant atelectasis or a focal consolidation (i.e. pneumonia)
  • Lactic acidosis: Common (up to 83% in one study) in patients with status asthmaticus admitted to the PICU. The vast majority of lactic acidosis was Type B (associated with adrenergic stimulation) (Meert, PCCM 2012) 
    • Type A: Due to impairment in oxygen delivery. Associated with lactate/pyruvate ratio >25
    • Type B: Due to adrenergic stimulation (i.e. high dose albuterol, epinephrine, etc.)


  • Oxygen: correct hypoxemia for O2 saturations >90%
  • Inhaled Beta-2 agonists: Work on airway smooth muscles, leading to bronchodilation (Camargo 2003, Karpel 1997, Travers 2001)
    • Albuterol (Can be given continuously generally maxing out at ~ 0.5 mg/kg/hr). 50:50 mixture of R (active enantiomer) and S albuterol (may not be completely inert and may cause tachycardia)
    • Levalbuterol (R enantiomer of albuterol) and thought perhaps to lead to less cardiovascular effects such as tachycardia although the evidence is not not clear
  • Corticosteroids: reduce inflammation (McFadden 2003, Rachelefsky 2003, Rowe 2004): NHLBI Guideline dosing (prednisolone, methylprednisone, etc.) 1-2 mg/kg divided BID. Doses of 1 mg/kg IV Q6 hrs are often used in the PICU
  • Ipratropium Bromide: anticholinergic agent, 0.25-0.5 mg nebulized in the ED reduced need for hospitalization and produces additional bronchodilation (Plotnick 2000 and Castro-Rodriguez 2005). In hospital use of ipratropium bromide has failed to demonstrate a significant benefit although it is still often used for severe exacerbations in hospitalized children. Does not cross blood brain barrier so avoid central anticholinergic effects. However, can get mydriasis if you get topical absorption (ie "blown" pupil in your status asthmaticus patient)
  • Theophylline/Aminophylline: phosphodiesterase inhibitor, increasing the levels of cAMP and thereby producing bronchodilation. 5.7 mg/kg loading dose followed by an infusion of 0.5-1 mg/kg/hr with levels checked q12 hours and goal 10-15 mcg/ml. Not recommended in NHLBI guidelines but still often used. No difference between theophylline and terbutaline except theophylline cheaper (Wheeler, PCCM 2005). Narrow therapeutic window. Aminophylline is equivalent to 80% theophylline. Can be associated with vomiting, nausea, fever, seizures 
  • Magnesium: Leads to smooth muscle relaxation (exact mechanism unknown but perhaps increases Ca2+ uptake in sarcoplasmic reticulum and functions as a calcium antagonist). Dosed 25-75 mg/kg up to 2g IV. Reduced hospiatlization rates in ED patients (Ciarallo 1996, Cheuk 2005, and Rowe 2000). Some studies (Okakama 1987 and Fesmier 1993) suggest a Mg level of 4.7 mEq/L is required to promote bronchodilation, leading some to utilize magnesium infusions (i.e. 20 mg/kg/hr with levels checked q6 hrs and goal Mg levels ~3-4 mEq/L). Can get hypotension, nausea, flushing 
  • Terbutaline: intravenous beta agonist: leads to bronchodilation, may be useful if due to cooperation or poor airflow/deposition, inhaled beta agonists are not effective (can sometimes evaluate response to inhaled beta agonists by looking at the heart rate, and if a sustained heart rate response is noted, then the patient is likely having some systemic absorption of inhaled beta agonists). Wheeler et al showed no difference except for increased cost when comparing terbutaline to theophylline. Typically dosed 0.1 to 10 ug/kg/min (usual starting dose ~ 1 ug/kg/min)
  • Heliox: Mixture of helium and oxygen of various blends: (80% Helium/20% Oxygen, 70% Helium/30% Oxygen, etc.). Helium, due to decreased density, reduces the Reynold's number, thereby helping to promote laminar flow (Reynold's number <2000) instead of turbulent or transitional flow (Reynold's number >4000 and 3000-4000, respectively). There is less airway resistance as a result of this laminar flow and thus, decreased work of breathing. The more helium, the more effective but in some patients, you may be limited in the amount of heliox you can deliver as they may require 50% FiO2 to maintain oxygen saturations. Some clinicians feel that below 60% Helium, there is little to no effect although theoretically, any helium should reduce the Reynold's number and promote improved flow dynamics. Found to improve gas exchange in patients with airway obstruction (Cheifetz 2005)
  • Noninvasive ventilation: Use of BiPAP has been described to improve work of breathing in patients with status asthmaticus (Fernandez 2001)
  • Ketamine: Dissociative sedative agent that leads to bronchodilation (blocking NMDA receptors in airway smooth muscle). Has theoretical benefit for sedative induction for intubating asthmatic patients and sometimes used for providing sedation to asthmatic patients but no clear evidence in unintubated patients (Howton 1996, Macias 2005). Also has side effect of bronchorrea, causing increased secretions which can be a significant issue with asthma. Dosed as bolus of 1-2 mg/kg IV and an infusion of ~ 1-2 mg/kg/hr. Concurrent use of benzodiazepenes may attenuate agitation/hallucinations/emergence delerium seen in older patients
  • Inhaled Anesthetics: inhaled anesthetics are potent bronchodilators (i.e. sevoflurane) but require specialized scavenging equipment and consultation with anesthesia. These have been used in the PICU on occasion
  • ECMO: VV ECMO is a very efficient way to clear CO2 and while rarely used for asthma, can be life saving and generally has excellent outcomes (~78% survival in this group of patients with asthma refractory to other treatments)

Intubation/Mechanical Ventilation

  • Intubation occurs in a small number of asthmatic patients admitted to the PICU (4-10% with significant variability)
  • No clear indications and largely based on clinical judgment
  • Ketamine often preferred anesthetic due to bronchodilatory effects. Avoid morphine due to histamine release and potential worsening of the inflammatory process. 
  • Can consider succinylcholine (rapid depolarizing muscle blocker) but more commonly, rocuronium used
  • Generally avoid bag mask ventilation 
  • Have fluid to give boluses on hand as institution of positive pressure ventilation in a dehydrated patient with elevated PVR can lead to hypotension
  • Avoid rapid respiratory rates as this can lead to worsened dynamic hyperinflation, higher lung volumes, hypotension, and pneumothorax
  • Ventilator settings: Permissive hypercapnea with pH >7.2 is generally well tolerated and preferable to overventilation with its risks of significant dynamic hyperinflation and subsequent barotrauma
  • Often times, pressure support is used to allow the patient to trigger their own breaths and determine their own inspiratory and expiratory times. A low mandatory respiratory rate is set with careful attention to the inspiratory time and I:E ratio (often needs to be 1:3-4 or greater)
    • One option is PRVC at 8 cc/kg, tolerating peak pressures of up to 45 cm H2O and aiming for plateau pressures <30 cm H2O with a low/physiologic respiratory rate with an I:E of 1:4 or greater. PEEP is set at 0 if neuromuscularly blocked or 1-2 cm H2O below measured AutoPEEP (up to ~ 8 cm H2O) if not neuromuscularly blocked (see PEEP discussion below)
  • Peak inspiratory pressures likely reflect a large degree of airway resistance (as well as the distending pressure needed to inflate the lung- this is the pressure used for dynamic compliance
  • Plateau pressures reflect alveolar pressures (more important when considering barotrauma) and are obtained by performing an inspiratory hold while in a volume control mode. This allows all airflow to stop and the pressure you measure is just the pressure needed to keep the lungs inflated-this is the pressure used to calculate a static compliance
  • The Peak to Plateau or "Delta" represents the pressure needed to overcome airway resistance and should improve over time if your patient's airway resistance is improving. 
Figure 2: Peak to Plateau Pressure and Airway Resistance

  • PEEP: Use of PEEP is controversial. If there is dynamic airway compression , PEEP may actual move the equal pressure point (between airway pressure and extrinsic pressure) so that airway collapse does not occur
    • AutoPEEP is measured with an end expiratory hold and reflects the degree of positive pressure and air trapping within the lung 
    • Setting the PEEP below the measured AutoPEEP can relieve dyspnea by facilitating ventilator triggering
    • If paralyzed, use of PEEP leads to higher lung volumes and increased airway and intrathoracic pressures and may actually be detrimental 
  • Monitor expiratory flow on the ventilator to ensure that flow returns to zero (ie expiration actually stops) before the next breath is initiated. Otherwise, you get incomplete exhalation with subsequent breath stacking and air trapping. 
Figure 3: Air trapping as seen on Flow vs. Time curve (Expiratory flow does not get back to baseline)

  • ETCO2 monitoring can also demonstrate bronchoconstriction and airway obstruction. 
    • The PaCO2- ETCO2 gradient reflects dead space ventilation and should improve as there is less airway obstruction and West Zone I type lung units
    • The ETCO2 waveform should be square. When it ramps instead, this is an indication of different lung units emptying at different times, which occurs with bronchoconstriction and airway obstruction. Thus, squaring of the ETCO2 tracing correlates with improved airway obstruction.
Figure 4: EtCO2 tracing in the setting of worsening airway obstruction 


1) M. Yung, M. South: Randomised controlled trial of aminophylline for severe acute asthma. Arch Dis Child.79:405-410 1998
2) M.O. Turner, K. Noertjojo, S. Vedal, et al.: Risk factors for near-fatal asthma. A case-control study in hospitalized patients with asthma. Am J Respir Crit Care Med.157:1804-1809 1998
3) R.C. Strunk, D.A. Mrazek, G.S. Fuhrmann, et al.:Physiologic and psychological characteristics associated with deaths due to asthma in childhood. A case-controlled study. JAMA. 254:1193-1198 1985
4) B.D. Levy, B. Kitch, C.H. Fanta: Medical and ventilatory management of status asthmaticus. Intensive Care Med.24:105-117 1998
5) A.J. Buda, M.R. Pinsky, N.B. Ingels Jr., et al.: Effect of intrathoracic pressure on left ventricular performance. N Engl J Med. 301:453-459 1979
6) Meert KL, McCaulley L, Sarnaik AP. Mechanism of lactic acidosis in children with acute severe asthma. Pediatr Crit Care Med. 2012 Jan;13(1):28-31
7) Stephanopoulos, R. Monge, K.H. Schell, et al.:Continuous intravenous terbutaline for pediatric status asthmaticus. Crit Care Med. 26:1744-1748 1998
8) R.W. Katz, H.W. Kelly, M.R. Crowley, et al.: Safety of continuous nebulized albuterol for bronchospasm in infants and children. Pediatrics. 92:666-669 1993
9) N.J. Gross: Ipratropium bromide. N Engl J Med.319:486-494 1988
10) D. Craven, C.M. Kercsmar, T.R. Myers, et al.:Ipratropium bromide plus nebulized albuterol for the treatment of hospitalized children with acute asthma. J Pediatr. 138:51-58 2001
11) R.A. Silverman, H. Osborn, J. Runge, et al.: IV magnesium sulfate in the treatment of acute severe asthma: a multicenter randomized controlled trial. Chest.122:489-497 2002
12) L. Ciarallo, A.H. Sauer, M.W. Shannon: Intravenous magnesium therapy for moderate to severe pediatric asthma: results of a randomized, placebo-controlled trial.J Pediatr. 129:809-814 1996
13) O.A. Akingbola, N. Simakajornboon, E.F. Hadley Jr., et al.: Noninvasive positive-pressure ventilation in pediatricstatus asthmaticus. Pediatr Crit Care Med. 3:181-1842002
14) M. Aubier, A. De Troyer, M. Sampson, et al.:Aminophylline improves diaphragmatic contractility. N Engl J Med. 305:249-252 1981
15) V.K. Gupta, I.M. Cheifetz: Heliox administration in the pediatric intensive care unit: an evidence-based review.Pediatr Crit Care Med. 6:204-211 2005
16) I.K. Kim, E. Phrampus, S. Venkataraman, et al.:Helium/oxygen-driven albuterol nebulization in the treatment of children with moderate to severe asthma exacerbations: a randomized, controlled trial. Pediatrics.116:1127-1133 2005
17) C.S. L’Hommedieu, J.J. Arens: The use of ketamine for the emergency intubation of patients with status asthmaticus. Ann Emerg Med. 16:568-571 1987
18) J.D. Tobias, J.S. Garrett: Therapeutic options for severe, refractory status asthmaticus: inhalational anaesthetic agents, extracorporeal membrane oxygenation and helium/oxygen ventilation. Paediatr Anaesth. 7:47-57 1997
19) C.H. Scoggin, S.A. Sahn, T.L. Petty: Status asthmaticus. A nine-year experience. JAMA. 238:1158-1162 1977
20) T.E. Stewart, A.S. Slutsky: Occult, occult auto-PEEP instatus asthmaticus. Crit Care Med. 24:379-380 1996
21) R.C. Wetzel: Pressure-support ventilation in children with severe asthma. Crit Care Med. 24:1603-1605 1996
22) D. Bohn, N. Kissoon: Acute asthma. Pediatr Crit Care Med. 2:151-163 2001
23) R. Stein, G.J. Canny, D.J. Bohn, et al.: Severe acute asthma in a pediatric intensive care unit: six years’ experience. Pediatrics. 83:1023-1028 1989