MCC ICU Topic Deep Dive: Status Asthmaticus 

Definition: Also known as acute severe asthma, status asthmaticus is defined as severe asthma not responsive to beta-agonist therapies. 

Risk Factors: Hx of asthma, respiratory infections, allergen exposure, air pollution, chemical exposure or inhalation, severe stress, cold weather, smoking. 

Symptoms: Wheezing, dyspnea, chest tightness, confusion, tripoding, accessory muscle use, tachypnea, hypoxemia, hypercarbia. 

Pharmacologic Treatment: inhaled beta agonist (albuterol), inhaled anticholinergic (ipratropium), epinephrine (IM/IV),  IV steroids,  inhaled corticosteroids, leukotriene antagonist (Montelukast) 

Nonpharmacologic: Heliox,  Bipap, mechanical ventilation, ECMO 

Guidelines: If someone can find a guideline for acute severe to critical status asthmaticus, please let me know. There are asthma guidelines and plenty of resources, but no official step by step guidelines that I can find for ICU level asthma. The following steps are obtained from a great video/ slideshow on lifeinthefastlane.com called “How to not kill an asthmatic”. I highly recommend watching! https://litfl.com/severe-asthma-management/

Mechanical Ventilation for Severe Asthma. Chest. 2015. Jun:147(6):1671-1680.

DOI 10.1378/chest. 14-1733

Mechanically Ventilating the Severe Asthmatic. Intensive Care Med. 2018 Sep: 33(9): 491-50. DOI 10.1177/0885066617740079

Management: Let’s assume that your patient has taken all of the above pharmacological treatments for asthma, but they still are in obvious respiratory distress. You now have several options to keep them safe while you wait for their asthma exacerbation to respond to treatment. 

Just a quick note. The issue with ICU level asthma is breath stacking and hypercarbia. Severe bronchospasm causes a limited ability to breathe in and even more limited ability to breathe out. As a result, you keep holding onto an increasing volume of air, leading to auto-peep. This means less ventilation as air cannot effectively move in and out (dead space/CO2 rising), and increasing intrathoracic pressure (Can be measured with inspiratory hold, resulting in high plateau) on inhalation and high intrinsic peep (Can be measured with expiratory hold). Too much pressure results in potential barotrauma (pneumothorax), decreased venous return to the heart and increased pressure on the RV to overcome thoracic pressure increase.  This can result in obstructive shock (bradycardia, hypotension, death) 

                                                                     OPTIONS

1. Repeat or trial IV epinephrine if not already given. This is an incredibly potent beta 2 agonist and will result in bronchodilation, thus opening your airways. Keep in mind, when you give inhalers to an asthmatic, a lot of that medication may not even be reaching the target area as a result of the asthma itself. Tachycardia and hypertension IS NOT a reason to withhold this option. 
2. Heliox. Heliox is a mixture of oxygen and helium (Instead of what we are are currently breathing, i.e. Nitrogen, oxygen, and CO2 with minor amounts of other gases mixed in). The data on this is somewhat mixed, but in theory if you provide “less viscous air”, this will allow better ventilation and potentially better delivery of inhaled medications into the airways that need it. I have attached a couple studies below. 
3. Treat anxiety. This is a natural response to not being able to breath, but it leads to worsening hyperventilation which leads to the dangerous part of severe asthma attack: Breath stacking. Ketamine might be a good option here as it typically does not lower your blood pressure (which could be mistaken for shock) as well as causes bronchodilation. Fentanyl and precedex are also reasonable options but keep in mind the hemodynamic issues they cause (lower BP for fentanyl and bradycardia for precedex) that both could precipitate and arrest in an asthma patient. 
4. Bipap. There are two goals here. One, your patient is going to get tired and weak if they have been in respiratory distress all day. Bipap will help diminish the work of breathing while you wait for your other therapies to kick in. Two, as your patient is breathing out, their airways are spasming and may collapse. By gently applying positive pressure to these airways you can splint them open so that the patient can exhale (and inhale) more effectively. Start with a low setting (8-10 over 5), but you are going to have to sit there and watch how your patient reacts. You want them to appear more comfortable and you want them breathing both in AND OUT easily. Breathing out especially can be an issue for these patients. 
5. Intubation. This should be avoided if at all possible, but also should be done before the patient is crashing. Warning signs would include increasing somnolence (CO2 rising would be the concern), and patient desaturation (was at 98% all day, now at 92%). There are a couple things to know here. 
6. 
   

First, hang a liter of isotonic fluids and let them rip. Active status asthmaticus have a lot of insensible loss and become dry quickly. If the asthma has been worsening over any considerable amount of time, eating and drinking are difficult prior to coming in. You are about to induce sedation with BP lowering medications and adding positive pressure (ventilator) to a system that already likely has a positive pressure problem (Air trapping).  Their BP is likely to tank on induction. 

Second, if you are reading this, you are not intubating this patient. There is no time for a miss and there is no second chance. Your best available person will intubate. 

Third, once intubated, go gentle with the bagging. You want that patient to exhale more than inhale at this point. Give them time to take a breath out. Barotrauma and pneumothorax are of major concern for this patient population. 

Fourth, you want deep sedation post intubation. These patients need to be synchronous with the ventilator so that you can determine reasonable vent settings and adjust for high plateau pressure. Your peak pressures are going to be high, but this is not a number that you should fixate on. Turn the alarm limits up and expect them to run high. Ketamine and propofol cause bronchodilation and may be an ideal starting point for deep sedation.  If your patient is resistant to sedation or fighting against the ventilator, paralytics are a reasonable option. 

Fifth, ventilator settings. Start with a low respiratory rate. These patients are going to be hypercarbic and the temptation is going to be a higher RR to blow off CO2. For asthma, this will compound the problem. They don’t need to breathe more….they just  need to breathe out effectively.. They will need a longer expiratory time and the lower the ventilator rate, the wider the I/E ratio. Six to seven ml/kg is a reasonable starting point. Start with low peep….if they are intubated in severe asthmaticus, they are often auto-peeping. Lifeinthefastlane suggests a peep of 3. Last, increase your flow rate to 80 LPM. The breath going in should be as fast as possible to allow a longer time for air to come out. This is going to make your peak pressures higher, but again, the peak pressure is not deadly. 

Sixth, you have to sit there and watch your patient. Have one of our MD’s there with you until you are comfortable with the ventilator, but you are trying to slowly titrate the vent until there is no more air trapping. See the image below.  

                          Please Refer to the Ventilator Waveform Picture Above 

Notice on that second line, before the patient’s expiration returns to 0 (the flat line) a new breath takes off. This will lead to air being stuck in the lung, or air trapping. Since that air is not ventilating, you are creating more dead space, or air that is not participating effectively in gas exchange. This leads to CO2 retention and high plateau pressures. 

1. Don’t get excited about hypercarbia. Your ABG is going to show respiratory acidosis until the asthma itself is responding to treatment. Meanwhile, tolerate a pH that is 7.15 or better. These tend to be younger patients and will tolerate this in the short term. Also remember, sodium bicarbonate breaks acid down into H2O and CO2. You will likely already have a CO2 problem and having them breathe better is really the ideal solution to the problem. 
2. Worst case scenario, refer the patient for ECMO. Most of these patients will turn around relatively quickly (24-48 hours), but for refractory acidosis, (pH < 7.15 persistently or hemodynamically unstable) this may be a reasonable option. Should your patient code, take them off the ventilator and push down on the chest to force exhalation. Your epi and albuterol both will drive serum potassium down so get labs quickly and watch your lytes. Your patient has been auto-peeping and they are at extremely high risk for pneumothorax so make sure this is not why they are coding with a chest x-ray. 
3. Consider PEEP matching if the patient tolerates. There is some controversy surrounding this and not a lot of evidence that I was able to find,  but theoretically this may make some sense. You need the patient to be synchronous with the ventilator to try this. Start with a low PEEP, let's say 3 as recommended above and do an expiratory hold. For example, let’s say your PEEP is at 3, but your expiratory hold reveals a pressure of 12. This means the patient has an extrinsic PEEP of 9 from their asthma. Slowly raise your PEEP with a goal of about ¾ of your initial result (for this patient, we are targeting a PEEP of 9). Repeat an expiratory hold and see what happens. If your expiratory hold now reads 18, this is not working and you are potentially hurting this patient. However, if your expiratory hold still says 12, then perhaps the end expiratory pressure you are leaving in the patient is not making the patient worse, but possibly is helping prop airways open, thus allowing better ventilation. Again, online I am finding arguments for both sides of this and this should really be done with caution and will need constant monitoring. 

The following article (Credit to Andy Zane here!) explores PEEP, AutoPeep, and how to manage! The take home point from Dr. Zane on this one is sometime’s PEEP is the answer, and sometimes it kills your patient. https://www.ncbi.nlm.nih.gov/books/NBK441904/

PHARMACOLOGY 

Beta Agonist: 

Albuterol (Inhaled): Beta 2 agonist, when inhaled results in direct smooth muscle relaxation from the trachea to the terminal bronchial tree. Has an onset of action 5-15 minutes with a half life of 3-4 hours  Prolonged treatments (1 hour) are available. 

Epinephrine: Potent beta 2 agonist (Beta 1 and Alpha as well). Can be given IV (0.1-0.25 mg) slowly once. An intramuscular dosing is available, but typically IV access is not an ICU problem. Onset of action is < 30 seconds when given IV with a half life of less than 5 minutes. 

Anticholinergic:  

Ipratropium: Anticholinergic, used in combination with albuterol (Duoneb). Actively blocks muscarinic receptors resulting in smooth muscle dilation. Onset of action 15-30 minutes with a half life of about 1.6 hours. 

Supplements: 

Magnesium: Electrolyte supplement that leads to potential smooth muscle relaxation. Typically 2-3 mg IV provided. The Internet book of critical care website  mentions a rather low amount of evidence for this (Study attached below) but in the end, this is cheap, harmless, and  easy to administer. 

Steroids:

Dexamethasone: 6-10 mg IV daily. Glucocorticoid with a half life of 3-4 hours in the plasma, but has a biological half life of 36-54 hours. Causes potent inflammatory inhibition and decreases swelling and mucous production in the airways. 

Methylpredinsolone:  60-80 mg IV 3-4 times daily with initial dose of 125 mg IV. Half life of 2.5-3.5 hours with long biological half life (12-36 hours). Causes potent inflammatory inhibition and decreases swelling and mucous production in the airways.

Prednisone: 40 mg PO daily. Biologic half life 12-36 hours. Causes potent inflammatory inhibition and decreases swelling and mucous production in the airways.

Serotonin Receptor Antagonists and Reuptake Inhibitor (SARIs) 

Trazadone: PO route only, 25-50 mg nightly to promote sleep. Half life 5-10 hours.  Monitor QT, metabolized in the liver. 

Medications to avoid: 

Long acting benzodiazepines, sedating antihistamines, opiates (unless pain is present), sedatives, hypnotics, barbiturates (unless alcohol withdrawal present)   

Random Dan Advice: 

• Work with your ICU MD for the first few asthmatics that hit the ICU. Most asthmatics respond quick to treatment and never reach the ICU, making our experience with them limited. These patients are in serious danger and making a wrong move could easily lead to a fatality. 
• Recognize that normal numbers might be a sign of danger. Someone who is breathing really fast and trying to breathe deep should not have a pH of 7.38. That is a sign of someone barely keeping up and a crash is imminent unless their asthma treatment suddenly kicks in. 
• Before you are treating a vented asthmatic, take advantage of the deeply sedated ventilator patients you are already taking care of. Get in the habit of checking plateau pressures (Inspiratory hold) and expiratory pressures (expiratory hold, should be equal to your PEEP if the patient is breathing out all of the way). 

Recent evidence for/against some of the above: 

FYI: not much to find in way of trials for ICU level as it is hard to randomize severe asthma patients for interventions

 A Multicenter Randomized Trial Assessing the Efficacy of Helium/Oxygen in Severe Exacerbations of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2017 Apr 1;195(7):871-880. doi: 10.1164/rccm.201601-0083OC.  

 This study used Heliox for 72 hours on COPD exacerbation patients. 445 patients participated with the trial stopping early for an overall low global failure rate. Heliox improved RR, pH, and PCO2 faster than routine cares, but did not prevent intubation or have any impact on 6 month mortality. There was no difference in the rate of non-invasive ventilation.  

. 1999 Aug;116(2):296-300. doi: 10.1378/chest.116.2.296. 

 Admittedly a very small trial, 23 patients randomized to 70/30 heliox or 30% FiO2. Peak Expiratory Flow was measured at intervals after admission with 58.3% increase in predicted PEF in the heliox group and only 10% increase in the oxygen group 

 A Pilot Prospective, Randomized, Placebo-Controlled Trial of Bilevel Positive Airway Pressure in Acute Asthmatic Attack. Chest. 2003 Apr;123(4):1018-25. doi: 10.1378/chest.123.4.1018. 

 Of 124 asthma patients in the ED setting, 30 were determined to have severe attacks and were randomized with half receiving Bipap and standard care and the other 15 patients receiving standard of care. . A goal of 50% increase in FEV(1) compared to baseline on admission was the goal of therapy. 80% of the bipap patients and 20% of the non-bipap patients achieved this goal