Two important studies for palliative care

Margaret Gibbs
Author: Margaret Gibbs
Category: Cancer, Conditions
Date: March 30, 2020

You may have already seen these articles, which really add to our understanding and management of two aspects of palliative care. Here are some salient points from both:

1. Hydration and symptoms in the last days of life

We observe that people have a reduced oral intake at the end of life due to their symptoms or general weakness and level of consciousness. There is inconclusive evidence that artificial hydration is beneficial, with arguments against being the chance of it increasing the likelihood of oedema, ascites and death rattle. Arguments for are that it may alleviate feelings of thirst and reduce the risk of agitation. There is also still opposing views on whether it prolongs the dying process. Palliative care providers tend to regard artificial hydration as an unnecessary burden at the end stage of life but other care givers and family members may feel differently.

A group of Dutch clinicians working at the Erasmus University Medical Center in Rotterdam carried out a multicentre prospective observational study to investigate the extent to which the amount of fluid intake preceding and during the dying phase is related to the occurrence of death rattle and terminal restlessness. They looked at 371 patients and reported that death rattle was reported at least once in 149 (40%) of this number. Terminal restlessness was reported in 96 (26%) of patients and was not associated with a lower amount of fluid intake however, terminal restlessness during the final 24 hours of life was associated with a higher amount of fluid intake, i.e. >250mL in 24 hours during the 25-48 hours before death.

They used the Back et al scoring scale to record the volume of death rattle (0 = inaudible to 3 = clearly audible from the door of the room and the Vancouver Interaction and Calmness Scale to measure restlessness (1 = calm to 5 = patient is pulling at lines/tubes) asking observers to report on a 6-point Likert scale (strongly agree to strongly disagree).

They concluded that caution with fluid intake to prevent development of death rattle does not seem to be necessary but a higher amount of fluid intake – possible over-hydration – during the last two days of life may contribute to terminal restlessness in the last 24 hours of life and that actively providing dying patients with artificial fluid may not be beneficial.
This study could provide a useful reference point for discussions within teams and possibly with families.

Lokker et al., Hydration and symptoms in the last days of life, BMJ Supportive and Palliative Care, accessed online January 2019

2. Cannabinoids for adult cancer-related pain

Four palliative care doctors from the north of England have carried out a systematic review and meta-analysis of the evidence regarding the effectiveness of cannabinoids for adult cancer pain. Interest in the use of this group of compounds has grown considerably since their high profile in the press and the change in legal status of some.

The authors identified over 2,800 records which yielded six RCTs involving 1,442 participants. They were able to include five in their systematic review and noted all had a low risk of bias. They found there was no difference between the change in pain score between the cannabinoids and placebo but cannabinoids carried a higher risk of adverse events (compared to placebo), especially somnolence and dizziness.

Five of the studies were using Sativex and four of these were with patients having advanced cancer which was not responding to optimised opioid doses. One studied patients with neuropathic pain. The last study was a comparison of THC:CBD in a combinations, THC alone and placebo.

The primary focus of the systematic review was change in pain intensity and the forest plot shows no difference between cannabinoids and placebo for the difference in change in average numerical rating pain scores. All studies reported on adverse events including those mentioned above (drowsiness and dizziness) but also hallucinations, euphoria, nausea and vomiting, and diarrhoea. There was an average 20% drop out during the study for those on active treatment plus a considerable and variable percentage in the placebo groups for the different studies.

The authors conclude that from the evidence available, it is not currently possible to recommend the addition of cannabinoids to the current treatments available for managing cancer pain.

As we know, the legality for prescribing cannabinoids was changed in 2019, mainly in response to one high-profile case of a child with intractable epilepsy. Doctors on the Specialist Register may prescribe medicinal cannabis in very specific circumstances, but the availability of suitable prescription products has been slow to follow on. Nabilone (THC) and Sativex (CBD and THC) have been available for some years but Epidyolex is a new CBD product recently approved by the EMA for the treatment of two seizure syndromes.

The NHS guidance confirms the outcome of the systematic review in saying there is currently not enough evidence to advise the use of cannabinoids for pain. Cannabis in its natural form contains around 480 identifiable chemicals, 80 of which have been identified as cannabinoids. It is worth mentioning that this review focuses on only the two licensed cannabinoids but future research may identify other active compounds that help to explain why some people report that cannabis helps their pain.

Boland E et al., Cannabinoids for adult cancer-related pain: systematic review and meta-analysis, BMJ Supportive and Palliative Care, 2020; 0; 1-11

Ashtons can provide a training session on cannabis oil. Please speak to your visiting pharmacist to book.

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