Question 4

A 30-year-old patient with life-threatening asthma is intubated and mechanically ventilated in your ICU. Bronchospasm persists despite treatment with inhaled salbutamol and ipratropium bromide, intravenous hydrocortisone, antibiotics, and magnesium.


a) List four additional pharmacological therapies that could potentially acutely improve this patient’s bronchospasm.    (2 marks)
b) List the advantages and disadvantages of their use.    (8 marks)
 

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College Answer

Syllabus topic/section:

2.1.5    Respiratory Intensive Care – L1.
2.1.21 Applied Pharmacology in Intensive Care.

Aim:
To explore adjuvant strategies for bronchospasm control for the severely critically ill asthmatic patient.
Discussion:
Candidates received higher marks if they were able to list pharmacological agents which would improve bronchospasm. Some candidates mentioned therapies which do not improve bronchospasm and were focused on other aspects of asthma care.
Adjuncts to the treatment of asthma such as muscle relaxants are not bronchodilators and hence did not gain marks. Inhalational Anaesthetics agents, intravenous ketamine, parenteral beta agonists (including adrenaline), or theophylline/aminophylline were acceptable therapies.
Majority of the candidates lost marks when they could not correctly list disadvantages of many of these agents, provided insufficient detail or had incorrect answers. This indicates a knowledge gap for a condition which is commonly seen in ICU.
 

Discussion

The second "list" question has eight marks attributed to it, which means it called for extensive detail. The question overall gives the impression that a table would have been the most appropriate answer format. The college have eliminated inhaled salbutamol, which implies that the intravenous option could still be discussed as an "additional" therapy. The remaining options therefore are:

  • Intravenous salbutamol
  • Methylxanthines such as aminophylline
  • Nebulised or intravenous adrenaline
  • Nebulised  magnesium sulfate
  • Ketamine
  • Inhaled volatile anaesthetic

Helium-oxygen mixtures, though they are a well-known strategy, are not listed here because they do not bronchodilate per se, which means they would not have scored marks. 

Anyway: to tabulate these with their advantages and disadvantages:

Advantages Disadvantages
Intravenous salbutamol
  • Overcomes the challenge of delivering nebulised salbutamol to distal bronchi in patients with poor inspiratory airflow
  • Does not rely on patient respiratory effort or coordination (i.e. appropriate in even the most dyspnoeic and uncooperative patients)
  •  
  • Potent proarrhythmic and chronotrope
  • Hyperlactataemia
  • Hypokalemia
  • No evidence that it improves outcomes when compared to continuous nebs
  • Systemic absorption of continuous nebs is often as good as IV, in terms of blood levels
Methylxanthines such as aminophylline
  • Intravenous (not relying on respiratory effort)
  • Levels can be monitored
  • Theoretical synergistic effect with other bronchodilators
  • Potent proarrhythmic and chronotrope
  • Narrow therapeutic range
  • Many drug interactions
  • Lowers seizure threshold
  • Less effective as a bronchodilator, when compared to salbutamol and adrenaline
Nebulised or IV adrenaline
  • Potent bronchodilator
  • May have some immunomodulator effects, eg. it can reduce the respose of airway smooth muscle to histamine (Baldwin et al, 1994)
  • Vasoconstriction of the airway mucosa may reduce airway diameter in addition to the bronchodilator effect
  • Can be given IM or as a neb if there is no access
Nebulised magnesium sulfate
  • Well tolerated and widely available
  • The MAGNETIC trial suggests that there is additive benefit with other bronchodilators
  • Little adult data
  • No evidence that it is beneficial when added to IV magnesium replacement
Ketamine
  • Bronchodilation is an extension of the central sympathomimetic effects
  • May have an additive effect with other bronchodilators
  • Also provides sedation and analgesia
  • Haemodynamic effects are more favourable for unstable asthmatic patient
Volatile anaesthetic agents
  • Bronchodilation is by a mechanism which is additive to other bronchodilators
  • Highly effective as a bronchodilators
  • Also provide anaesthesia
  • Available in most centres
  • Increases the complexity of care without added benefit
  • Requires a different ventilator with vapouriser and scavenger system
  • May have adverse (hepatic, renal, haemodynamic) effects
  • Expensive if used for prolonged periods

References

rowne, Gary J., et al. "Randomised trial of intravenous salbutamol in early management of acute severe asthma in children." The Lancet 349.9048 (1997): 301-305.

Tobin, A. "Intravenous salbutamol: too much of a good thing?." Critical Care and Resuscitation 7.2 (2005): 119-127.

Salmeron, Sergio, et al. "Nebulized versus intravenous albuterol in hypercapnic acute asthma. A multicenter, double-blind, randomized study." American journal of respiratory and critical care medicine 149.6 (1994): 1466-1470.

Aralihond, A., et al. "Treating acute severe asthma attacks in children: using aminophylline.Breathe 16.4 (2020).

Yung, Michael, and Mike South. "Randomised controlled trial of aminophylline for severe acute asthma." Archives of Disease in Childhood 79.5 (1998): 405.

Carlsson, Jenny A., and Hannah K. Bayes. "Acute severe asthma in adults.Medicine 48.5 (2020): 297-302.

Littenberg, Benjamin. "Aminophylline treatment in severe, acute asthma: a meta-analysis." JAMA 259.11 (1988): 1678-1684.

Baldwin, David R., et al. "Comparison of the effects of salbutamol and adrenaline on airway smooth muscle contractility in vitro and on bronchial reactivity in vivo." Thorax 49.11 (1994): 1103.

Costello, Jonathan, and Marten Howes. "Nebulised magnesium in asthma.Emergency Medicine Journal: EMJ 21.5 (2004): 586.

Lew, Alicia, et al. "Volatile anesthetic agents for life‐threatening pediatric asthma: A multicenter retrospective cohort study and narrative review." Pediatric Anesthesia 31.12 (2021): 1340-1349.

Turner, David A., et al. "Isoflurane for life-threatening bronchospasm: a 15-year single-center experience." Respiratory care 57.11 (2012): 1857-1864.