Ray Corcoran

The Safety and Efficacy of a Single Dose (500 mg or 1 g) of Intravenous Magnesium Sulfate in Neuropathic Pain Poorly Responsive to Strong Opioid Analgesics in Patients with Cancer

Neuropathic pain may respond poorly to morphine and is often difficult to relieve. Recent attention has been drawn to the role of the N-methyl-D-aspartate (NMDA) receptor in the potentiation of neuropathic pain. Magnesium is known to block the NMDA receptor. It reduces the neuropathic pain response in animals, and attenuates postoperative pain and migraine in humans. We have examined the safety, tolerability, and efficacy of two intravenous doses of magnesium sulfate in 12 patients with neuropathic pain due to malignant infiltration of the brachial or lumbosacral plexus. The first six patients received 500 mg, the remainder 1 g. Apart from a mild feeling of warmth at the time of the injection, both doses were well tolerated. After receiving 500 mg, three patients experienced complete pain relief and two experienced partial pain relief for up to 4 hours duration; pain was unchanged in one patient. After receiving 1 g, one patient experienced complete relief and four experienced partial pain relief of similar duration; pain was unchanged in one patient. Intravenous magnesium sulfate in these doses appears to be safe and well tolerated. A useful analgesic effect may be obtained in some patients and further evaluation is warranted.

Descriptors of Breathlessness in Patients With Cancer and Other Cardiorespiratory Diseases

The objective of this study was to examine the relationship between descriptors of breathlessness and its underlying cause in patients with lung cancer and cardiopulmonary diseases to see whether descriptors might be used to help determine the cause of breathlessness, particularly in patients with lung cancer. We studied 131 patients with primary or secondary lung cancer, whose breathlessness was attributed to tumor mass, pleural effusion, lung collapse, metastases, pleural thickening or lymphangitis carcinomatosis, and 130 patients with breathlessness attributed to asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease or cardiac failure. Patients selected statements (descriptors) that described the quality of their breathlessness from a 15-item questionnaire and the relationship between the descriptors and the attributed cause of breathlessness was evaluated by cluster analysis. All patient groups were characterized by more than one cluster and several clusters were shared between groups. Specific sets of clusters were associated with breathlessness due to asthma, COPD and cardiac failure, and to cancer causing collapse, metastases or pleural thickening. The association of different sets of clusters with the different diagnostic groups suggests that patients are describing qualitatively different experiences of breathlessness, but the relationship does not appear to be sufficiently robust for the questionnaire to aid differential diagnosis.

Audit of three antimuscarinic drugs for managing retained secretions.

Clinical experience suggests that noisy retained secretions or ‘death rattle’ are commonplace in patients with cancer in the last few days of life. Retrospective reviews suggest an incidence of 34–70%, with most patients receiving either intermittent injections or a continuous infusion of hyoscine hydrobromide.1–4 Other antimuscarinic drugs such as hyoscine butylbromide and glycopyrrolate are used, as are repositioning and suction.5,6 There are no prospective studies published of the efficacy of any of these measures. Treatment is thus largely pragmatic and can vary even within a single centre. Nurses have expressed a desire for consistent clinical guidelines.6 We have therefore audited the effect of guidelines based upon the use of three different antimuscarinic drugs emphasizing the support of those in attendance.

Safety and efficacy of nebulized lignocaine in patients with cancer and breathlessness

Although anecdotal reports suggest nebulized lignocaine may help breathlessness in patients with cancer this has not been examined formally. We report a pilot study comparing nebulized lignocaine 100 mg and 200 mg with saline in six patients with cancer who were breathless at rest. Nebulized lignocaine was well tolerated apart from mild bronchoconstriction in two patients after the 200 mg dose and the unpleasant taste; serum concentrations were below levels at which toxicity has been reported. The effort of breathing (measured on a visual analogue scale) did not differ between treatments, whereas the distress of breathing was less after saline than after either dose of lignocaine. These findings do not support the reported benefits of nebulized lignocaine.

The importance of low magnesium in palliative care

We agree with Brogan et al. that magnesium deficiency can be important in palliative care, is probably underdiagnosed and so undertreated.1 Measurement of serum magnesium, however, is not always diagnostic, and we have found the magnesium loading test to be necessary if chronic magnesium deficiency is to be reliably diagnosed in palliative care patients. Both of the patients described by Brogan et al. had received platinum-based chemotherapy, which can quickly result in marked and sometimes protracted renal wasting of magnesium sufficient to cause symptomatic hypomagnesaemia. When magnesium deficiency develops more insidiously, serum magnesium, being under tight homeostatic control, is maintained whilst tissue stores are depleted. Indeed, in our survey of patients attending a palliative care unit, with multiple risk factors for deficiency, the incidence of hypomagnesaemia was low at only 3%.2 In the magnesium loading test an intravenous dose of magnesium sulphate is administered (based on the weight of the patient) followed by a 24 h urine collection to calculate the dose of magnesium retained by the patient. Probable magnesium deficiency is suggested by retention of more than 20% and definite magnesium deficiency by retention of more than 50% of the dose.3 Of the seven patients we have examined to date all have been shown to be definitely deficient (mean retention 76%, range 62–98%), despite serum magnesium levels within or above the normal range (mean 0.9 mmol/l, range 0.7–1.4 mmol/l). Thus, for many patients within a palliative care setting, serum magnesium is not the most reliable way of identifying chronic magnesium deficiency.4,5 Along with the magnesium loading test we are measuring serum ionized magnesium, urinary, red cell and white cell magnesium in order to find a simple, reliable and more readily available method of assessing chronic magnesium deficiency in palliative care patients.

Reading numbers aloud: a measure of the limiting effect of breathlessness in patients with cancer.

BACKGROUND Progress in the treatment of breathlessness at rest or on minimum exertion in patients with cancer requires a practical and valid method of measuring symptoms. A study was undertaken to explore the practicality, repeatability, and sensitivity of reading numbers as a form of exercise test in this group of patients. METHODS Thirty patients with cancer and 30 age matched healthy subjects read numbers aloud as quickly and clearly as they could for 60 seconds. After five readings the maximum number of numbers read and the number read per breath was noted. This procedure was carried out twice in one day and one week later to assess within and between day repeatability. The sensitivity of the test was assessed by making measurements in 13 patients with cancer before and after drainage of their pleural effusion. RESULTS The concept was easily understood by all subjects. Twelve patients were unable to complete five readings in all tests due to tiredness. Compared with control subjects patients read fewer numbers in the three tests (87-89% of control) and fewer numbers per breath (59-60% of control). Repeatability was good both within and between days. After drainage of their effusion all patients were less breathless and there was an increase in both the maximum number of numbers read (23%) and the number read per breath (60%). CONCLUSIONS The number of numbers read and the number read per breath over 60 seconds was practical, easy to carry out, showed good repeatability within and between days and was sensitive to the improvement seen following drainage of a pleural effusion. It may be a useful measure of the limiting effect of breathlessness in this group of patients.