Importance of Magnesium in Palliative Medicine

In our daily clinical practice we pay little or no attention to magnesium (Mg) as a source of many troubles and symptoms in palliative medicine. However, this may rapidly change. Recently, a vigorous discussion on the meaning of hypomagnesaemia took place in our palliative medicine discussion list * and in this issue of Progress in Palliative Care two interesting articles on the use of Mg in palliative care are listed (1,2). Another Ietter on Mg will be published soon (3). Let us take a doser look at the role of Mg in palliative medicine. Mg is an important intracellular cation required in many cellular energy metabolism processes, membrane stabilisation, nerve conduction, ion transport and calcium channel activity (4). Only 1% of total body Mg is found extracellularly, so in many situations, measuring plasma Mg levels may not reflect actual state of total body Mg. However, this is truer for the acute electrolyte derangements. In chronically-ill patients, low plasma Mg (Jess then 0.75 mmoi/L) clearly herald Mg deficiency. On the other hand, normal plasma Mg may be found in many deficient states, so a Mg loading test may be necessary for reliable diagnosis of hypomagnesaemia (5). In the magnesium loading test, an intravenous dose of magnesium sulphate is administered (based on the weight of the patient) followed by a 24-hour 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 Crosby et al. (3) examined to date, all have shown to be definitely deficient (mean [range] retention: 76 [6298]%) despite serum magnesium levels within or above the normal range (mean [range]: 0.9 [0.7-1.4]mmoVI). Hypomagnesaemia is more frequent in patients with other electrolyte derangement and may occur together with hypocalcaemia and hypokalaemia. Poor Mg intake, due to anorexia, rapid intestinal transit time e.g. due to 5-FU/folinate-induced diarrhoea, persisting renal tubular damage due to cisplatin chemotherapy, previous irradiation of abdominal organs and prolonged use of diuretics all may contribute to hypomagnesaemia at the end of life. Symptoms of hypomagnesaemia are unspecific but may include anorexia, muscle weakness, twitching, tremor, irritability, paresthesiae, ataxia, depression, confusion and arrhythmias. Crosby et al. ( 1) performed a pilot study administering Mg sulphate intravenously to 12 cancer patients suffering from neuropathic pain. Response to Mg sulphate was independent of plasma Mg and was perfectly safe. Useful analgesia was observed in a significant number of patients with the duration of approximately 4 hours. The observation that Mg may be therapeutic even in the absence of magnesium deficiency had been confirmed by others (6). Mg in the absence of deficiency is being also used in the treatment of pre-eclampsia, ischaemic heart disease, cardiac arrhythmias, urolithiasis and bronchial asthma. Mg is the chief cation blocking NMDA receptors, important in pain conduction (7) and is probably much Jess toxic than ketamine. However, in a previous study Mg was found to be Jess potent than ketamine (8). 1 wonder if hypomagnesaemia may influnce ketamine toxicity? To my knowledge, no studies in this field were done. In two cases recently reported (2), hypomagnesaemia caused mainly muscle weakness, twitching, fatigue and paraesthesias. All these symptoms improved after parenteral Mg therapy. However, (too) rapid infusion of magnesium sulphate intravenously may decrease magnesium reabsorption in the loop of Henle with most of the infused Mg tuming up in urine (4). For these reasons oral replacements are preferred, especially when the symptoms are mild or chronic. ln acute and severe cases 1 would recommend parenteral therapy. Oral Mg preparations are poorly absorbable mainly due to saturable bowel absorption (9). Mg which is not absorbed may be a useful laxative, although overuse of such oral preparations may cause troublesome diarrhoea. What are the )essons from the above? First of all, it is evident that Mg is important and its deficiency may be frequent and overlooked in terrninally-ill patients. Sorne symptoms, refractory to other therapy, may promptly respond to non-toxic and safe doses of parenteral Mg sulphate. We should not neglect Mg any more and start thinking about it while facing many difficult problems in palliative medicine. But be sure, Iike in many other cases, Mg alone will never solve all the problems of our patients.