Relief of acute dyspnea : no convincing evidence for opiates or benzodiazepines

27 Jan

While being sick at home and still working on diuretics in Acute Pulmonary Edema I thought to myself, why not post something I have already finished but never put on the internet. (Better lazy then tired as we say in Holland 😉 ) Sadly I found that most of it has to be translated into English, except for the following “poster”.

One of my great residents (Annemarie v/d/ Velden) was interested in morphine and benzodiazepines for the relief of acute dyspnea. Opiates have traditionally been used as one of the main treatments of acute dyspnea and are still recognized as such. Most current textbooks and official guidelines advise the use of morphine as one of the first-line treatments for patients in acute dyspnea and a majority of physicians accept it to be the case. Benzodiazepines are widely used for the relief of breathlessness in advanced diseases and are regularly recommended in the literature. For me this was something you never think about and it just works….but does it really???

Here is what we did and the results we found:

We performed an extensive literature search in order to validate the evidence for the use of opiates and benzodiazepines in acute dyspnea. An electronic search was carried out of Medline, Embase and The Cochrane Library. The primary search key used was dyspnea, the secondary and tertiary were morphine and benzodiazepine. Limits were set to Humans and Adults, and articles had to be published in English, German or Dutch. Review articles and reference lists of retrieved articles were hand searched. A total of four papers, all in English, were found that directly investigated or reported the clinically important outcomes of treatment of acute dyspnea. Two of these papers were Cochrane Collaboration Review Articles, both relatively recently updated. The full text of the relevant studies were retrieved and data were independently extracted by the authors. Studies were quality scored according to the Oxford Quality Scale.

1.)
Jennings, el al (2002) was a review article with 18 RCT included and 293 patients with dyspnea of any cause.They looked at the effect of morphine (either nebulized, oral or parentally) The meta-analysis showed a statistically significant positive effect of benefit of non-nebulised opioids on the sensation of breathlessness, but the clinical effect appears to be relatively small. Although this effect is small, certain pharmacological aspects need to be considered, including the fact that (a) the opioid doses were relatively small in some of the studies; (b) the doses were not titrated in any of the studies; (c) the dosing intervals were probably too long in some of the studies; and (d) the opioids would not have reached steady state in the single dose studies.

2.)
Simon, et al (2010) was e review article with 7 RCT included and 20 patients with advanced stages of cancer, COPD, CHF, Motor Neurone Disease of Idiopatic Pumonary Fibrosis. They looked at the effect of benzodiazepines on dyspnea in patients with advanced disease and found no evidence for a beneficial effect of benzodiazepines for the relief of breathlessness in patients with advanced cancer and COPD. There is a slight but non-significant trend towards a beneficial effect but the overall effect size is small. Benzodiazepines caused more drowsiness as an adverse effect compared to placebo, but less compared to morphine.

3.)
Sosnowski MA, et al looked at the effect op opiods in Acute Pulmonary Edema and as I have said in a previous post they found no evidence supporting the use of opiates in APE! There appears to be a strong association with worse outcome.

4.)
Peacock WF et al. also looked at morphine in ADHF and found no benefit and morphine seemed to be associated with increased adverse events including mechanical ventilation, prolonged hospitalisation, more ICU admissions and higher mortality. It has to be noted that in this article it was unclear when the morhine was given, so there is a possibility it was given as sedation during intubation in some cases!

In conclusion it seems that:
– Current literature does not offer any solid evidence for the routine use of morphine or benzodiazepines for the relief of acute dyspnea.
– A slight but non-significant trend towards a beneficial effect of morphine has been reported, but the overall effect tends to be small.
-Morphine in APE shows no benefit and is likely to do more harm
– An increase in adverse events when using morphine for the relief of acute dyspnea has been reported, but the level of evidence offered is low.
– It seems that the use of morphine and/or benzodiazepines in the relief of acute dyspnea is mainly based on tradition and anecdotal evidence.

See you next time!

Egon Zwets

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