Abstract
Patient and drug regimen selection important with opioid use in advanced COPD, given adverse respiratory event risk http://ow.ly/LNXJ30bPD6C
To the Editor:
In the ancient Roman literary masterpiece Metamorphoses, the poet Ovid writes that the god of sleep, Somnus (who had a twin brother named Thanatos, or Death), lived in a dark cave and “in front of the cave mouth a wealth of poppies flourish” [1]. This verse demonstrates that our ancestors recognised links between sleep, death and the poppy plant (from which opium is derived). Present-day population-based studies show that opioid drugs are used frequently [2, 3] and in other potentially concerning ways [2] among individuals with chronic obstructive pulmonary disease (COPD), including those with nonpalliative disease [2]. Several guidelines [4–6] support using opioids for refractory respiratory symptoms in advanced COPD, which is a commonly encountered and challenging problem. The report by Politis et al. [7] in the European Respiratory Journal describes a case of respiratory depression in an individual with advanced COPD following receipt of prescription opioids for dyspnoea, providing a timely reminder of the serious negative respiratory effects opioids can potentially have in vulnerable COPD patients.
Several interesting points for discussion emerge from the case report. First, the timing of opioid drug receipt and the adverse event in the case is noteworthy. Although this patient with advanced COPD suffered from chronic, severe exertional dyspnoea (without frequent respiratory exacerbations), and although this is the precise clinical setting in which opioids have been evaluated and found to be efficacious [8–11], he did not receive opioids pre-hospitalisation. Instead, he first received opioids while hospitalised with a presumed acute infectious COPD exacerbation, which is a setting in which opioid therapy has not been evaluated [8–11] and at least one guideline makes explicit that opioids should be used “in stable patients” with advanced COPD [6]. However, he tolerated opioid therapy well and benefitted from it while in hospital for an acute infectious exacerbation, and opioid-related respiratory depression instead occurred 9 days following hospital discharge, when he was presumably in a more respiratory-stable state. The timing of the patient's opioid receipt and adverse event challenges current perceptions of when opioids can potentially be used in advanced COPD (i.e. only in the setting of stable chronic dyspnoea) and when adverse respiratory events can potentially occur (i.e. only if given during periods of respiratory status instability).
Second, the opioid regimen used in the case is interesting. It consisted of standing, twice-daily, long-acting, oral tablet morphine plus immediate-release, liquid morphine as required every 4–6 h for breakthrough. While this regimen consisting of both standing and pro re nata opioids may be commonly used in chronic pain or palliative care settings, its efficacy and safety have not been specifically examined for refractory dyspnoea management in COPD. Instead, two approaches to prescribing opioids for advanced dyspnoea in COPD are presently outlined in the literature (one formulated by a group of Australian physicians [10–11] and the other by Canadian physicians [6, 9]) and neither approach was used in this specific case. The “Australian approach” consists of once-daily, sustained-release, oral tablet morphine sulfate (10–30 mg) [10–11]. The “Canadian approach” consists of standing, immediate-release, liquid morphine sulfate (starting at 0.5 mg twice daily) with possible weekly up-titration based on clinical re-evaluation, followed by possible eventual substitution with a sustained-release preparation [6, 9]. While the latter Canadian approach is characterised by a more cautious introduction of opioids in the setting of advanced COPD, incorporating prudent elements of prompt and repeated patient re-evaluation, it is noteworthy that it involves, at least initially, giving immediate-release, liquid morphine, inadvertent misuse of which got the patient in this specific case into trouble [7]. Compared to tablet-formulation opioids, liquid morphine may be more challenging for patients to self-administer, as it requires cognitive skill to correctly calculate the amount of liquid to draw based on the liquid's concentration, as well as technical ability to correctly draw the prescribed amount of liquid.
Third, it is notable that the patient in this case unintentionally misused the immediate-release, liquid morphine prescribed despite receiving “verbal and written education…by a pharmacist prior to discharge” [7]. Even following his adverse respiratory event and further education efforts, he was still unable to safely self-administer immediate-release, liquid morphine. This highlights that in least in some patients, adequate drug counselling cannot overcome the risk of adverse events associated with unsupervised opioid drug self-administration at home. The fact that individuals with COPD tend to be older in age and have multiple comorbidities makes this group particularly vulnerable to potential opioid-related dosing error and toxicity.
While opioids can be effective at reducing troublesome refractory respiratory symptoms in individuals with advanced COPD, the report by Politis et al. [7] reminds us that adverse respiratory events associated with opioid drug use are real and potentially serious. While more research on this therapeutic approach is needed, in the interim, careful thought must be given to both patient and drug regimen selection if initiating opioids.
Footnotes
Conflict of interest: None declared
- Received March 7, 2017.
- Accepted March 17, 2017.
- Copyright ©ERS 2017