The Pharmaceutical Journal
Vol 279 No 7478 p568-569
17 November 2007

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Palliative Care Pharmacists Network

Is it the patient who benefits from treatment for the “death rattle”?

Christine Hirsch, based in the pharmacy department at Aston University, also provides a clinical pharmacy service to the Black Country Palliative Care Service and Compton Hospice in Wolverhampton. She recently completed a doctorate and shared the results of her research project on the use of antisecretory agents at the end of life.

A problem, referred to as “noisy ventilation”, “retained secretions” or the “death rattle”, has always existed but it is unknown whether it causes distress to dying patients or just to those around them (such as relatives and staff) as they die. Comparative research in this area has been inconclusive in finding evidence for efficacy of the most commonly used anticholinergics but there are additional issues.

The cause of the condition is uncertain — some believe it is due to movements of the soft palate rather than secretions, in which case, drugs will not help. We do not know anything about the harm from side effects of the drugs used in these circumstances and furthermore, if the patient is, as we believe, unaware and undistressed by the symptom, then is it ethical to administer drugs to one individual for the benefit of another?

Dr Hirsch’s research compared noise-meter scores after administration of the two most commonly used anticholinergic drugs in the hospices where she works. As is often the case in palliative care research, the quantity of patients in the study was small but broad conclusions were that stat doses of hyoscine hydrobromide were most effective and continuous infusion of hyoscine butyl bromide did not correspond with a subjective reduction in noise level.

Dr Hirsch said that pharmacology was an issue — salivation and bronchial secretions have complex enervation and so, perhaps, one anticholinergic should not be expected to be the answer. Further discussion is required over who is actually being treated when drugs are administered for death rattle and whether more research is needed.

Strategies for the use of NSAIDs in palliative care

Victor Pace, a consultant at St Christopher’s Hospice in London, has a particular interest in non-steroidal anti-inflammatory drugs (NSAIDs) and gave a picture of where things are now with this group of drugs, once widely prescribed in palliative care. He reminded listeners of how widely used these broad spectrum analgesics are with 30 million users daily worldwide, with their array of useful indications, their ease of administration and their relatively low cost.

In spite of good evidence in certain areas, the complications from peptic ulceration, small bowel problems, renal failure and thrombotic risk have accounted for around 1,000 hospital admissions and a 100 or so deaths per month. However, it should be possible to predict and manage the risk for individual patients and continue to use the safer NSAIDs at times when alternatives are not possible.

Dr Pace reviewed the mechanisms by which NSAIDs damage the gut. The COX hypothesis that blames gastric damage solely on the inhibition of the gastric protection mechanism may be flawed. It may be more than a coincidence that almost all NSAIDs are acidic and possible that their acidity attracts them to the phospholipids that form the mucus layer protecting the stomach, thus removing that protective layer.

Stomach acid reduction can help, but proton pump inhibitors are essential, especially where there is no alternative to NSAID therapy. The older antacids or H2 inhibitors are ineffective for this purpose.

Supplying the missing prostaglandin, using misoprostol is also effective but its side effects make adherence a problem. With its lower acidity, nabumetone seems to have a far lower incidence of perforation, ulceration or bleeding, which seems to uphold the theory that the COX effect alone may not account for gastric damage.

With respect to thrombosis risk, rofecoxib comes out as the most risky option while naproxen has the lowest relative risk for cardiovascular events.

With regard to renal safety, pre-existing conditions need to be considered. Patients with low circulating volume due to blood loss, dehydration, heart failure, severe diarrhoea or vomiting, or bleeding, for example, are in most danger of renal failure with NSAIDs.

Dr Pace concluded by recommending a strategy for the use of NSAIDs in palliative care. He suggested first considering non-pharmacological options and then if needed, weighing their use against an increased opioid dose, assessing risk factors individually for each patient’s potential complications and using gastro-protection.

Special attention needs to be paid to any patients at risk due to their renal function. Drugs should be avoided that score most highly in the risk tables and treatment should be stopped after two weeks if it proves ineffective.

Tramadol — a drug that raises a number of questions

Andrew Dickman, from the Marie Curie Palliative Care Institute in Liverpool, provided an exploration of tramadol — a drug that raises a number of questions in palliative care. The drug has been around for 30 years and is one of the most widely prescribed drugs in the world but opinions range over its efficacy and harmful effects, mainly due to ignorance regarding its complex pharmacology.

One of the main problems is that its absorption is dependent on p-glycoprotein, which shows wide genetic variability. It exerts its analgesic action via serotonin and noradrenaline reuptake inhibition and is also a weak agonist at the mu opioid receptors. Additionally, the positive and negative enantiomers of tramadol are dependent on cytochrome activity, which is subject to both inhibition and induction.

Thus, when tramadol is given in combination with such drugs as paroxetine, fluoxetine, haloperidol and levomepromazine, both the analgesia and adverse effect profile may be altered.

There is also the need to reduce doses or intervals in patients with renal or hepatic disease as tramadol is eliminated via both the kidneys and liver. Another hazard is the concomitant use of serotonergic drugs, which may lead to increased serotonergic side effects and possibly serotonin syndrome. Pharmacists are often asked for equivalent doses for increased analgesics in palliative care.

Dr Dickman warned against estimating any such equivalence for tramadol and opioids due to the variability of pharmacokinetics in the individual and, in the case of stopping tramadol in favour of a strong opioid, of the risk of monoaminergic withdrawal. His advice would be to cross taper or add in a strong opioid if further analgesia is required.

Managing drug errors in hospices

Margaret Gibbs, a pharmacist at St Christopher’s Hospice, spoke about the management of drug errors in hospices. Although the press may not reflect it, the culture has changed over the years from one of blame and individual admonishment to one centred on reviewing systems and improving procedures.

Documents such as “Building a safer NHS” (2004) and “Safety in doses” (2007) offer practical guidance and good examples, but some specific aspects of practice in palliative care may also be beneficial in reducing risk.

Palliative care differs from other branches of medicine in some ways. The primary goal in this specialty is high quality symptom control and occasionally, eagerness to respond to patients may make staff less efficient in following procedures. High doses of opioids are used regularly, of which there are many potentially confusing brands and formulations and syringe drivers that carry fewer safety features than modern infusion devices continue to be used.

“We know that a low rate of error reporting does not always mean we are working safely — it can indicate unwillingness to report. What we all aim for is a high rate of near-miss reporting, indicating awareness, but a minimal rate of critical incidents”.

Ms Gibbs described two critical incidents and the action taken. A patient was admitted on an insulin regimen but her recent blood sugar levels were not communicated clearly. A dose of long-acting insulin had been given, resulting in a serious hypoglycaemic attack that required intensive intervention. As a result, a new blood glucose monitoring form was developed and launched.

On another occasion, when alfentanil was fairly new to palliative care, a 24-hour dose of alfentanil was administered in error as a stat dose. There has been resistance to use conversion charts because they are based on data from single-dose studies and each patient and their drug history is different.

However, from the safety point of view, a conversion chart was then drawn up and accepted so that all staff could refer to this to check their calculations to ensure they were prescribing or administering a “reasonable” dose.

Some incidents are difficult to predict, for example, it was discovered that a family were administering medicines to their relative on the inpatient unit without informing staff. Also a mix-up occurred some time ago when a husband and wife were both under the care of one home care nurse.

A request to the GP for a new prescription was issued for the wrong partner. Now it is ensured that all requests are faxed and different clinical nurse specialists are allocated to different members of one family if that rare situation arises.

Using an estimated total number of drug administrations in the hospice, a figure has been calculated for error rates. At St Christopher’s Hospice, this has slowly decreased in the past eight years from 0.04 per cent to 0.03 per cent with some upward fluctuations in the past three years. It is ambitious to expect to create comparable figures in large hospitals to make comparisons.

Ms Gibbs hopes to encourage other hospice pharmacists to collect data in a similar format in order to bench-mark error rates and share examples of good practice.

PILs for drugs used in palliative care outside their licence

Ray Bunn works as a community pharmacist in Sussex and his pharmacy has a contract to provide services to St Catherine’s Hospice in Crawley. This has sparked his interest in palliative care and inspired him to embark on some inventive projects.

He has explored the possibility of becoming a pharmacist with a special interest. He defined the process for joining the scheme for listeners and showed how his own practice might fit in with the accreditation framework, although his local bid to become a pharmacist with a special interest has not been fruitful.

Mr Bunn shared his recent project, which involves creating a series of patient information leaflets (PILs) for drugs commonly used in palliative care outside their licence. This is something many have been aiming to do for some time since standard PILs can be misleading in such circumstances, leading to possible mistrust or non-adherence.

Additionally, the Healthcare Commission encourages informing patients when they are prescribed a drug for use outside its licence but the general feeling is that counselling conversations about this can sound more alarming than need be. Long-established drugs are used within recommended doses but for different indications, eg, haloperidol for nausea and vomiting.

Mr Bunn set up a multi-disciplinary group to write the leaflets (choosing the 13 most commonly used drugs) which will be attached to the existing PILs provided with all dispensed medicines. Future developments include posting the PILs on the St Catherine’s website to enable other organisations to share this work, to translate them into other languages and modify them for visually impaired patients, and to investigate ways in which other community pharmacists can use them.