Asthma is quite an interesting condition to treat acutely, not only because it is gratifying when patients get better rapidly (which most of them do) but also because they are a group that can deteriorate quickly and hide their signs of deterioration well given their young age and relative health.
Given the nature of the disease it is not uncommon for patients to feel much better after being treated down in ED, then get worse again on the ward, perhaps as the frequency of their B agonist therapy is reduced. It is therefore imperative to avoid the common pitfalls when called to see these patients on the ward. The information below is directed at adult patients, but a lot of it will also apply to paediatrics too.
Asthmatics can die quickly
If you look at near fatal asthma cases two distinct phenotypes emerge as seen in the table above- the group that worsens over several days and whose pathology involves mainly mucus plugging, and the group who mainly develops bronchoconstriction with very rapid deterioration but faster responses to therapy. The latter are more commonly known as brittle asthmatics.
It is this group that are particularly relevant to ward calls as respiratory failure can develop in as little as 2 hours, and death is often sudden and unexpected (1). Such patients often show marked diurnal variation in peak flow, especially a large dip in the early morning, even when their previous peak flow was normal (1). Looking back at a patient’s previous discharge summaries and clinic letters should help you identify who might fit into the “sudden onset” phenotype.
In hospital death is not related to admission findings but is related to the phenotypes above
A paper from 1977 (2) provides the only analysis that I could find of arrests occurring in asthmatics in hospital. Out of 1345 admissions there were 10 arrests amongst 9 patients, with 3 deaths. All but one arrest occurred on the general ward.
The findings are highly interesting- 8/10 arrests occurred between midnight and 0600. The risk of in hospital arrest bore little relation to the findings on admission, including tachycardia, pulsus paradoxus, peak flow, hypokalemia, blood gas findings, or history of status asthmaticus. In general the patients presented initially with mostly mild attacks, which explains why most of them were on the general ward rather than an ICU/HDU.
The only variable that was associated with in hospital arrest, and which was present universally in all patients who arrested, was a diurnal variation in peak flow > 50% while on the ward, which is presented nicely in the graph below of one patient’s peak flows.
Therefore the only variable predicting in hospital arrest was a feature of the “sudden onset” phenotype we discussed above. It is worth keeping in mind that this study was conducted in 1977 when treatments might have differed substantially. All my googling, however, indicates that salbutamol was available in Britain by the 1970s, and it is clear from the paper that steroids were widely used.
Do not attribute tachycardia to the effects of salbutamol
The presence of tachycardia is more closely related to the severity of asthma rather than the effects of Beta agonist treatment. High dose beta-agonists actually result in a fall in the heart rate when they exert significant bronchodilatory effect and when used in the treatment of severe asthma (3). This is because bronchoconstriction and hypoxia are often the main drivers of tachycardia. Asthmatics can also become volume deplete as they lose a lot of fluid through the airways when tachypneic.
Salbutamol definitely has an effect on the heart rate but this is smaller than often imagined. In one study mild asthmatics received 2, 6, then 18 puffs of salbutamol at 90 minute intervals, resulting in a maximum average increase in the heart rate of only 8 beats per minute (4). In healthy volunteers, escalating doses of 4,6, then 8 puffs at 15 minute intervals failed to produce a heart rate rise more than 8 beats per minute (5). In ICU patients who received salbutamol for any reason the maximum response was 4 bpm in those without pre-existing tachycardia and 2 bpm in those with baseline tachycardia (6).
Hypoxia is an indicator of life-threatening asthma
The presence of SpO2 < 92% defines an asthma attack as life-threatening according the British Guidelines (7). After dealing with so many COPDers on your time on general medicine, you might get used to seeing wheezy hypoxic patients and not bat too much of an eyelid. Asthma is a different beast.
While your COPDer may happily float around at home with saturations of 90% because of their chronically destroyed lungs, asthmatics tend to have normally functioning lungs at baseline so hypoxia implies significant airway compromise. While the risk of CO2 retention is low at saturations above 92%, obtaining an ABG is recommended when the saturation falls below this (3).
On the note of ABGs
Initially an arterial blood gas should show a respiratory alkalosis as the asthmatic lung still excels at eliminating CO2. Over a few days the kidneys will start to excrete bicarbonate to compensate resulting in a fall in the bicarbonate level.
The transition to a normal CO2 in someone with an ongoing exacerbation signifies clinical deterioration as the respiratory muscles are now getting fatigued. An elevated CO2 signifies severe deterioration and is a reason for ICU transfer.
A metabolic acidosis may result from the previous renal compensation of eliminating bicarbonate, or from lactic acidosis from respiratory muscle fatigue. A metabolic acidosis is a sign of imminent respiratory arrest (1).
Other signs of imminent arrest (1)
- Bradycardia or fall in heart rate despite clinical state not improving
- Paradoxical breathing (diaphragm goes up during inspiration and down during expiration)
- Disappearance of wheeze
- Feeble or exhausted respiration
- Hemodynamic instability
It is always tempting to see a patient looking anxious and ascribe a lot of their presentation to anxiety. This is because the human brain likes to opt for an easy way out, an easy explanation for things. Incidentally, the medico-legal literature is full of cases where this happens. “Oh, he looks worse than he is because there is a large element of anxiety”.
Quite aside from the fact that suffocating to death is highly anxiety provoking, anxiety is also a physiologic response to hypercapnia (8). Therefore the response to an anxious looking asthmatic is to look for worsening airflow limitation or hypercapnia, or at least be happy that these are not likely.
Prescription of sedatives such as benzos and zopiclone is associated with increased mortality in asthma exacerbations (9,10).
Wheeze is NOT a reliable indicator of severity
Perhaps the most common pitfall, which I have saved till last, is assuming that severity of wheeze is related to the severity of the attack. Neither the duration of wheeze in proportion to the respiratory cycle nor the loudness of the wheeze bear any relation to the severity of the attack or the degree of airflow limitation (11). Wheezing may be quite loud in mild cases where airways are widely patent, or it may be near absent in severe bronchoconstriction. I will never forget a young child I saw in ED with severe asthma whose only finding on auscultation was reduced air entry on the left side.
We have covered some common pitfalls in the detection of the deteriorating asthmatic, where early detection can be paramount to a good outcome.
- Near-fatal asthma: recognition and management. Ruben D. Restrepo and Jay Peters. Current Opinion in Pulmonary Medicine 2008, 14:13–23.
- Asthma: analysis of sudden deaths and ventilatory arrests in hospital M R HETZEL, T J H CLARK, M A BRANTHWAITE British Medical3Journal, 1977, 1, 808-811
- Asthma exacerbations· 5: Assessment and management of severe asthma in adults in hospital. S Aldington, R Beasley – Thorax, 2007 – thorax.bmj.com
- Bronchodilator, cardiovascular, and hypokalaemic effects of fenoterol, salbutamol, and terbutaline in asthma. S.WongMBI. D.PavordMRCPJ. WilliamsBAJ. R.BrittonMDA.E. TattersfieldFRCP(Prof)The Lancet. Volume 336, Issue 8728, 8 December 1990, Pages 1396-1399
- Thorax 1989;44:136-140 Cardiovascular and hypokalaemic effects of inhaled salbutamol, fenoterol, and isoprenaline JULIAN CRANE, CARL BURGESS, RICHARD BEASLEY From the Department ofMedicine, Wellington School of Medicine, Wellington, New Zealand
- Changes in Heart Rate Associated With Nebulized Racemic albuterol and levalbuterol in Intensive Care Patients. Sum Lam, Julie Chen. Am J Health Syst Pharm. 2003;60(19).
- SIGN 153 • British guideline on the management of asthma A national clinical guideline September 2016
- Activation of the Orexin 1 Receptor is a Critical Component of CO2-Mediated Anxiety and Hypertension but not Bradycardia. Philip L Johnson et al. Neuropsychopharmacology volume37, pages1911–1922(2012) doi:10.1038/npp.2012.38
- Risk factors for death in patients admitted to hospital with asthma: a follow-up study.G. Ryan et al. Internal Medicine Journal. Volume 21, Issue 5 October 1991. Pages 681–685
- Pharmacoepidemiol Drug Saf. 2015 Aug;24(8):793-802. doi: 10.1002/pds.3799. Epub 2015 May 27. Association between benzodiazepine use and exacerbations and mortality in patients with asthma: a matched case-control and survival analysis using the United Kingdom Clinical Practice Research Datalink. Nakafero G1, Sanders RD2, Nguyen-Van-Tam JS1, Myles PR1.
- ERS Handbook of Paediatric Respiratory Medicine. edited by Ernst Eber, Fabio Midulla