Slack- Refractory Status Asthmaticus: Drips & Gases & ECMO, Oh My!

Today we are happy to welcome Dr. Donald Slack, A second year Pulmonary-Critical Care fellow here at the University of Maryland. He hails to us most recently from Christiana Health Care System where he completed his internal medicine residency before returning home to UMMC, where he spent his medical school training. Today he shares some information extracted from a VERY difficult asthma case that presented to his service several months ago. This is a fantastic review of the random things we attempt to keep asthmatic airways open. So before you reach for that EpiPen or start the ketamine drip, you should take 45 minutes and learn about why those ideas may not be as helpful as you think.


Clinical Pearls- Dr. Donald Slack


  • Acute asthma exacerbation is a complex mechanism with multiple inflammatory pathways
  • Status asthmaticus is a common admitting diagnosis to the medical intensive care unit.
    • Outside the usual cocktail of treatment (e.g., steroids, bronchodilators, ventilator support if needed), numerous adjunctive therapies are often utilized without great evidence.

Advanced treatment modalities:

  • Epinephrine Infusion
    • Evidence: largely retrospective chart review on ED safety profiles
      • Associated with ~30% “minor events” and 3% “serious events,” without a clearly demonstrated therapeutic impact
    • Alpha-agonist therapy (e.g., phenylephrine) in asthma demonstrated worse airway resistance in all but more severe cases.
      • Perhaps this is why epinephrine (non-selective agonist treatment) may not be useful
    • GINA 2015 guidelines suggest not using epinephrine for acute asthma exacerbation unless associated with anaphylaxis or angioedema
  • Heliox
    • Unclear effect on nebulized drug delivery to the distal airways
    • Probably has its greatest impact by reducing work of breathing in non-intubated patients by improving laminar flow (remember the Reynolds Number = R) by reducing the density of the gas being inhaled (see below)
      • Decreases Ppeak in paralyzed and mechanically ventilated patients, but its therapeutic impact is unclear
    • Guidelines suggest “there may be some benefit” before intubation, but no evidence for use in intubated patients


  • Ketamine
    • Bronchodilator effect probably mediated by inhibition of muscarinic acetylcholine (M1) receptors in the lung
      • Two small, fairly well-designed prospective studies suggest that it is not useful in acute severe asthma
    • Guidelines make no meaningful comments on the subject
  • Inhaled Anesthetics
    • Decades of case reports and case series in the literature suggest a therapeutic benefit in patients refractory to all other interventions
    • Guidelines agree that they “might be useful”
  • ECMO / ECCO2R (Extracorporeal CO2 Removal)
    • Growing body of case reports supporting ECMO for hypercapnic respiratory failure
    • CESAR trial had ~9 hypercapnic patients randomized to ECMO or SOC
      • Unfortunately, no subgroup analysis was performed on these patients, so impact on morbidity or mortality for this indication is unknown
    • Compared to ECMO, ECCO2R uses a smaller, pump-less circuit (i.e., uses patient’s own cardiac output to drive flow) and smaller arterial and venous catheters
    • One small Italian study utilized ECCO2R in COPD patients prior to intubation and observed a lower intubation rate and improved mortality
    • This is definitely an area of future research – stay tuned!

Suggested Reading

  1. Schivo M, Phan C, Louie S, Harper RW. Critical Asthma Syndrome in the ICU. Clin Rev Allerg Immuno. 2015; 48:31-44.[PubMed link]
  2. Leatherman J. Mechanical Ventilation for Severe Asthma. Chest. 2015; 147(6):1671-1680. [PubMEd Link]
  3. Del Sorbo L, Pisani L, Filippini C, Fanelli V, Fasano L, Terragni P, Dell’Amore A, Urbino R, Mascia L, Evangelista A, Antro C, D’Amato R, Sucre MJ, Simonetti U, Persico P, Nava S, Ranieri VM. Extracorporeal CO2 removal in hypercapnic patients at risk of noninvasive ventilation failure: A matched cohort study with historical control. Crit Care Med. 2015; 43(1):120-127.[Pubmed Link]
  4. GINA 2015 Guidelines[Ginasthma Link]
  5. ATS 2013 Guidelines[ATS Link]
About the Author

Jim Lantry

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Just your average critical care doc: Wandering the ED and ICUs for the USAF down in the San Antonio Military Medical Center, traveling the globe to cannulate for ECLS wherever the need arises, and trying to keep up with great minds of today. E:

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  1. Deepak Kadiyala

    Revisited your talk after a similar patient presented to our ICU and knew where to find the info. Thx for a great talk

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