October 2005

Dear Readers: Here's the Article for this Month:

Name of article:

Low dose diamorphine reduces breathlessness without causing a fall in oxygen saturation in elderly patients with end-stage idiopathic pulmonary fibrosis

Author(s): Allen S, Raut S, Woollard J, Vassallo M.
Abstract:  Palliative Medicine 2005; 19: 128-130

Idiopathic pulmonary fibrosis (IPF), also known as cryptogenic fibrosis alveolitis, is a non-malignant pulmonary disease, the incidence of which increases with age. The patients with IPF have a poor prognosis (mean survival of 2 years from the time of diagnosis in patients over 75). There are no specific effective therapies except for heart-lung transplantation. There is present a relatively high respiratory drive and patients suffer from severe dyspnea and anxiety in the end-stage of the disease.

To evaluate the efficacy and tolerability of diamorphine in the treatment of dyspnea, the authors carried out an open observational study in 11 elderly, opioid naïve, distressed patients (mean age 86 years, range 78-92, there were eight females and 3 males). The patients had no significant cognitive impairment and experienced severe dyspnea at rest due to the end-stage IPF and most of them had intermittent cough and disturbed sleep.

Among the opioids, diamorphine via the subcutaneous route was chosen because it was habitually used in the hospital and because of its absorption characteristics and its predictable peak effects within 30 minutes.

The patients were not receiving steroids or other drugs able to modify their pattern of ventilation. They received supplemental oxygen therapy to attempt to have at least a 94% oxygen saturation before start ing the study. All patients had a low performance status: they required hoist transfers or nurse-assisted transfers; the mean Activities of Daily Living (ADL) index was 5/20 (range 1-8); and the mean time from the initial diagnosis of IPF was 4.6 years (range 3.1-11).

The following parameters were assessed just before and 15 and 30 minutes after the first subcutaneous injection of 2.5 mg diamorphine (10 patients), or 5 mg (1 patient with a body weight over 60 Kg):

• intensity of dyspnea assessed by means of 100 mm Visual Analogue Scale (VAS)

• heart rate and respiratory rate

• systolic blood pressure

• oxygen saturation by pulse oximetry

• levels of anxiety and agitation observed and recorded by the nurses

The intensity of dyspnea decreased from a VAS of 83 mm at baseline to 36 at 15 (p<0.0001) and at 30 minutes after diamorphine administration; the heart rate decreased from 99 beats/min to 87 at 15 (p= 0.007) and 86 at 30 minutes after opioid administration. Anxiety and agitation were reduced in all patients. A small non-significant reduction was also observed in oxygen saturation (the largest individual fall in PaO2 was 3%), systolic blood pressure decreased from 115 to 109 mmHg and respiratory rate from 22 to 20 breaths/min.

After the reduction of symptoms was observed due to diamorphine, all patients were treated with controlled release oral morphine and the therapy was then tailored according to the patients’ needs. Some of them were switched to short release oral morphine at doses of 20 to maximum of 60 mg/day. Some patients required diamorphine via continuous subcutaneous infusion later in the illness.

No patient had respiratory depression. Seven patients survived an additional 5 weeks and four patients were discharged to nursing homes.

Why I Chose this article

There is very little data available in the literature about the efficacy and safety of opioids in the management of dyspnea in an elderly population with advanced and terminal cancer and with non-malignant end-stage pulmonary diseases. Moreover, there is again (still) the fear of opioid induced respiratory depression and a reluctance to use opioids for the treatment of dyspnea in the context of elderly patients with non-oncological diseases such as in idiopathic pulmonary fibrosis (IPF). This observational study may be considered a pilot study on the efficacy and tolerability of diamorphine and oral morphine in a population of very frail elderly patients with dyspnea, anxiety, and agitation due to end-stage a “non-malignant” condition such as IPF. The authors state that further research is necessary on a larger sample of patients treated over a longer period of time.

Carla Ripamonti, MD
Member of the Board of Directors, IAHPC