Updates on Asthma and COPD 2013

Updates on Asthma and COPD from Chew Keng Sheng

Presented during the 1st National Emergency and Critical Care Symposium in Ipoh, Perak, Malaysia, Nov 2013

Updates on asthma

It is important to remember that there are two separate classifications for any asthmatic patient that admits to the emergency department - one is with regards to the level of control of asthma over a prevailing period of time and secondly, the severity of the acute asthmatic attack in the A&E department itself.

1. For asthma control, a quick guide would be to apply the rule of 2:

Attacks of >2 times per week or
Needs rescuer inhaler of >2 times per week
Awakening due to nocturnal symptoms >2 times per month
Use >2 canisters of relievers per year
If yes to any = uncontrolled, needs steroids

2. Should we use continuous nebulized beta-2 agonist instead of intermittent nebulization?

“Continuous” neb = continuous aerosol delivery or sufficient frequency of at least 1 neb q15 min or >4 neb/hour.
In a Cochrane systematic review, Camargo et al (2009), 8 trials, n = 461, found that

• Continuous nebulization has greater benefits in severe disease, with
• Significant lung improvement at 2 – 3 hours
• And with similar side effects profile  in both arms (tremors, increased K+, HR), which are
• Well tolerated

Reference:
Camargo Jr CA, Spooner C, Rowe BH. Continuous versus intermittent beta-agonists for acute asthma. Cochrane Database of Systematic Reviews 2003, Issue 4. Art. No.: CD001115. DOI: 10.1002/14651858.CD001115

3. Does IV beta-2 agonists offer any advantages over nebulized beta-2 agonists?

Travers et al (2001), in a Cochrane systematic review, (15 trials, n = 583) show that IV beta-2 agonists offer no therapeutic advantage over inhaled forms of the drugs. However, no difference in autonomic side effects between the two arms.
Reference:
Travers A, Jones AP, Kelly K, Barker SJ, Camargo CA, Rowe BH. Intravenous beta2-agonists for acute asthma in the emergency department. Cochrane Database Syst Rev.2001;(2) :CD002988

4. How early should IV steroids be given?

Rowe et al (2009), in a separate Cochrane systematic review (12 trials, n = 863) show that IV steroids given within 1 hour:

• significantly reduced admission rates (OR = 0.40, 95% CI: 0.21 to 0.78)
• And its benefits are most pronounced among those with severe asthma and in those who have not yet been on systemic steroids prior to ED presentation

Reference:
Rowe BH, Spooner C,Ducharme F, Bretzlaff J, BotaG. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database of Systematic Reviews 2001, Issue 1. Art. No.: CD002178. DOI: 10.1002/14651858.CD002178.

5. How about anticholinergics use in asthma?

Anticholinergics should not to be used alone. In a pediatric Cochrane review, Teoh et al (2012) (4 trials, n = 171) show that anticholinergics alone less efficacious and more likely to fail.

On the other hand, Griffiths et al (2013), in another systematic review (15 trials, n = 2497) involving pediatrics population, found that combining anticholinergic and SABA significantly reduces the risk for hospital admission

References:
Teoh L, Cates CJ, et al. (2012). Anticholinergic therapy for acute asthma in children. Cochrane Database Syst Rev 4: CD003797.

Griffiths B, Ducharme FM. Combined inhaled anticholinergics and short-acting beta2-agonists for initial treatment of acute asthma in children. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD000060. DOI: 10.1002/14651858.CD000060.pub2.

6. What is the role of Magnesium sulphate in asthma?

The postulated mechanism of action of magnesium sulphate in asthma is the blocking of the calcium channel, and thereby it relaxes bronchial smooth muscle. It also inhibits the contractile response to endogenous bronchoconstrictors. Rowe et al (2009) in a separate systematic review  involving a small number of 7 trials with n = 665 show that

• overall there is no improvement in lung function
• no improvement in admission rate with the use of magnesium sulphate.
• BUT magnesium sulphate has been shown to reduce admission rate in severe asthma subgroup.

Reference:
Rowe BH, Bretzlaff J, Bourdon C, Bota G, Blitz S, Camargo CA. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. Cochrane Database of Systematic Reviews 2000, Issue 1. Art. No.: CD001490. DOI: 10.1002/14651858.CD001490.

7. Is the evidences for NIPPV use in asthma as strong as in COPD?

No.
Although Lim et al (2012) in a Cochrane review (5 trials, n = 206) with preliminary results show NIPPV has benefit of

• Reduced hospitalization rate
• Time to discharge from ED
• Improves lung function

But the review shows that the use of NIPPV still lacks of good evidence and its use remains controversial. Therefore, it is not recommended for routine use.

In fact, two of the studies demonstrated that 2 intubations were needed in the 45 participants on NPPV vs no intubations in 41 control patients (risk ratio 4.48; 95% CI 0.23 to 89.13).

Reference:
Lim WJ, Mohammed Akram R, Carson KV, Mysore S, Labiszewski NA, Wedzicha JA, Rowe BH, Smith BJ. Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma. Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: CD004360. DOI 10.1002/14651858.CD004360.pub4.

8. When would we need to consider mechanical ventilation for an asthmatic attack?

According to Brenner et al (in 2009 in Proceedings of the American Thoracic Society)
there are four indications for mechanical intubation:

• cardiac arrest
• respiratory arrest or profound bradypnea
• physical exhaustion
• AMS (agitated patient, interfering with oxygen delivery)

Note that: Hypercapnia per se without evidence of physical exhaustion or mental changes IS NOT an indication although persistent hypercapnia despite treatment +/- AMS is an  indication (this is defined as a PaCO2 increase of ~ 5mmHg/Hr or more than 55 – 70 mmHg)

One should also allow for permissive hypercapnia in order to minimize risk of increased intrathoracic pressure, and thereby, the risk of barotrauma.

Therefore, the initial ventilation settings should be:

• Tidal Volume (TV) 6 ml/kg
• Rate 6/min
• I:E up to 1:4

Try to keep the Plateau pressure (Pplat) below 30 cm H20. If your plateau pressure is too high, adjust the minute ventilation (i.e., lower the TV or rate)

Pplat (or lung distension pressure) gives an estimate of average of end-insp alveolar pressure. In other words, it is a surrogate indicator for lung compliance.

Reference:
Brenner B, Corbridge T, and Kazzi A. Intubation and Mechanical Ventilation of the Asthmatic Patient in Respiratory Failure, in Proceedings of the American Thoracic Society, Vol. 6, No. 4 (2009), pp. 371-379.

Induction agent.
Many induction agents can be used for endotracheal intubation, but one of them is ketamine.
Properties of ketamine
releases of catecholamines
bronchial smooth muscle relaxation
Side effects – hypersecretion, hypertension, arrhythmias, and hallucinations
relatively contraindicated in patients with ischemic heart disease, hypertension, increased intracranial pressure.

Updates on COPD

1. What is the recent update with regards the concept of COPD?
COPD should no longer be considered just as a pulmonary disease. It should be considered as a systemic disease (Agusti, 2005) as it involves a lot of systemic inflammation, systemic oxidative stress, activation of circulating inflammatory cells, e.g. neutrophils, macrophages, and augmented levels of pro-inflammatory cytokines. A lot of extrapulmonary associations with COPD such as : IHD, osteopenia, cachexia, malnutrition, skeletal wasting. That’s why it is so important to build up the muscle bulk and nutrition status of COPD patient.

Reference:
Agusti AG. Systemic effects of chronic obstructive pulmonary disease. Proc Am Thorac Soc 2005; 2 (4):367-70; discussion 71-2.

2. What about the use of bronchodilators in COPD?

In a Cochrane systematic review, McCrory et al (2005) said that there is

• No significant difference in changes in FEV1 between b2-agonists and the anticholinergic ipratropium at 90 minutes and 24 hours and
• no advantage combining

However, in view that anticholinergics have slower onset (15 min, peak 60 to 90 min, and longer 6 to 8 hrs), the general consensus regarding the use of bronchodilators according to the GOLD guidelines, for practical purposes, is SABA first, then anticholinergics.

Reference:
McCrory DC, Brown CD. Anticholinergic bronchodilators versus beta2-sympathomimetic agents for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD003900. DOI:10.1002/14651858.CD003900.

3. What are the evidences on the use of NIV in COPD?

Unlike in asthma where the evidences are lacking, the evidences for the use of NIV in COPD  are much stronger.

In a Cochrane systematic review, for example, Ram FSF et al (2004) (14 trials involving n = 622 for outcome of treatment failure, and n = 541 for the outcome of mortality) show that NIPPV resulted in

• decreased mortality
• decreased need for intubation
• reduction in treatment failure

Reference:
Ram FSF, Picot J, Lightowler J, Wedzicha JA. Non-invasive positive pressure ventilation for treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2004, Issue 3. Art. No.: CD004104. DOI: 10.1002/14651858.CD004104.pub3.

4. What about the use of mechanical ventilations in COPD patients?

There are a number of delicate issues with the use of mechanical ventilation in COPD patients (Brulotte et al, 2012) including:

• poorer prognosis (mortality rates between 20% and 73%)
• a mean life expectancy of 1 year
• Barotrauma, infections

These issues should be discussed with the patients and their family members.

Reference:
Brulotte CA, Lang ES. Acute exacerbations of chronic obstructive pulmonary disease in the emergency department. Emerg Med Clin North Am. 2012; May;30(2):223-47, vii.

5. How real is the fear of hypoxic drive in COPD?

Many clinicians would have known the issue of hypoxic drive in COPD patients. The concept of hypoxic drive basically says that because COPD patients are chronically exposed to high level of CO2 in the body, the central respiratory centre is no longer sensitive enough to CO2 (desensitized to high level of CO2); and therefore the body has to depend on low level of PaO2, sensed by the peripheral chemoreceptors, to drive the respiration.

But, actually how real is this fear?
If we go deep into the literature, we find that it all started off with a paper by E.J.M Campbell in 1960 in Lancet. Much of what people wrote for guidelines and recommendations was based on anecdotal and experience reports. There is really not much science behind it! It was mainly consensus opinions rather than meta-analyses and systematic reviews.

In fact, in a Cochrane review, Austin Wood-Baker (2009),
“No relevant trials have been published to date, so there is no evidence to indicate whether different oxygen therapies in the pre-hospital setting have an effect on outcome for people with acute exacerbations of COPD”

Although this Cochrane review is done for a prehospital context, the concepts remain similar. There is no significant effect demonstrated that different FiO2 given would result in different outcomes of a COPD patients.

One study that came close in demonstrating hypoxic drive would be the study by Plant et al (2000). This study shows an association between increased oxygen with hypercapnea, respiratory acidosis, and ICU admission but even then, this does not occur in every patient given increased FiO2.

References:
Austin MA, Wood-Baker R. Oxygen therapy in the pre-hospital setting for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD005534. DOI: 10.1002/14651858.CD005534.pub2.

Plant PK, Owen JL, Elliot MW. One year period prevalence study of respiratory acidosis in acute exacerbations of COPD: implications for the provision of noninvasive ventilation and oxygen administration. Thorax 2000;55:550–4.