CORRESPONDENCE |
Magnesium sulphate and ischaemic heart disease
* E-mail: subodha_6r{at}yahoo.co.ukEditor—We read with interest Wadhwa and colleagues'1 paper about the use of magnesium sulphate to reduce the shivering threshold. We question whether there is any potential ‘real world’ use for this proposed therapy of high-dose magnesium in patients with myocardial ischaemia, either peri-infarction, periangioplasty or perioperative coronary bypass graft surgery.
We agree that shivering is undesirable due to the increased oxygen consumption and can increase the risk of myocardial ischaemia. However, putting such a frail population, who are already in a compromised cardiovascular state, at the perils of high-dose magnesium infusion seems in contradiction to their best interests.
Magnesium can cause heart block, the risk being higher in patients who are already on calcium or beta receptor antagonists.2 Treatment with magnesium by continuous infusion can cause severe muscle weakness. This effect is significant when serum levels >2 mg litre–1, especially patients who are in renal failure. Specifically in the postoperative cardiac surgery population, there are other detrimental effects such as profound recurarization in patients who were treated with magnesium sulphate even at lower doses (60 mg kg–1) after 1 h of recovery of vecuronium block.3 Magnesium can also increase the incidence of postsurgical bleeding by inhibition of platelet function and antagonizing calcium function on the clotting cascade.4 5
We use magnesium, given as a single 2–5 g slow i.v. infusion to reduce cardiac irritability after cardiac surgery in most of our patients. In a recent prospective audit of 110 postoperative cardiac surgery patients, we found 25% of postoperative patients were shivering with a mean core temperature of 36.3 (range 34.6–38°C), despite sedation with morphine and low dose propofol. We treat shivering patients with meperidine, and warm them appropriately as required. However, we are describing a population that is routinely mechanically ventilated after operation.
Maintaining magnesium levels at twice the normal level may not cause any detrimental effects in young, healthy volunteers. However, in sick patients the use of high-dose magnesium for the prevention of shivering is not practical. We wish the authors all the best with future research, which we suspect may be focused more on the patient at risk of cerebral ischaemia, rather than myocardial ischaemia.
London, UK
E-mail: agdoufas{at}louisville.edu
Editor—We would like to thank Drs Thanthulage and Stacey for their interest in our work. It is true that a relatively high, although not supra-clinical, dose of magnesium sulphate was used in our trial, which included young healthy volunteers.1 However, the purpose of this study was not to ‘propose a high-dose magnesium therapy in patients with myocardial ischaemia’, but to evaluate the potential of magnesium for inhibiting the normal thermoregulatory defenses to hypothermia in humans. In this type of study, usually done in healthy volunteers, it is common to adopt an escalating dose scheme or high-dose infusion in order to adequately characterize the dose–response relationship and identify the magnitude of the effect for the agent under evaluation. In addition, since the central nervous system (CNS) is the major site for thermoregulatory effect and magnesium demonstrates a low CNS bioavailability,6 a ‘high-dose’ approach was essential in the present experiment. Although various patient populations may respond differently to a particular agent or dosing strategy, it is worth noticing that the serum magnesium concentrations achieved in our study (1.89–2.21 mmol litre–1) were lower than those suggested for the treatment of eclampsia (2.0–4.0 mmol litre–1)7 and much lower than those producing respiratory (5.0–6.5 mmol litre–1) or cardiac (>7.5 mmol litre–1) toxicity.8 Interestingly, similar serum magnesium target concentrations (1–2 mmol litre–1) are currently used in clinical trials evaluating the neuroprotective properties of the agent in patients with subarachnoidal haemorrhage.9 10
Because of the excellent neuroprotective record of magnesium in animals, a corollary of our investigation is the potential use of magnesium to facilitate the application of therapeutic hypothermia11 in patients who suffer from neurological or myocardial ischemic injury. We have managed to exclude the possibility of magnesium use, as a sole agent, for that purpose. Nonetheless, a window remains open for the potential supplementary role of the agent to facilitate induced hypothermia. We certainly recognize the diverse and potentially serious complications of i.v. magnesium administration in sick patients. However, the range of dose and method of administration, as well as potential viable combinations with other agents are the objectives of ongoing and future trials in volunteers and various patient populations.
Louisville, USA
References
1 Wadhwa A, Senguptha P, Durani J, et al. Magnesium sulphate only slightly reduces the shivering threshold in humans. Br J Anaesth 2005; 94: 756–62
2 Pittman JAL. Magnesium sulphate for pre-eclampsia and a sudden bradycardia. Br J Anaesth 2000; 85: 327–8
3 Fuches-Buder T, Tassonyi E. Magnesium sulphate enhances residual neuromuscular block induce by vecuronium. Br J Anaesth 1996; 76: 565–6
4 Fawcett WA, Haxby EJ, Male DA. Magnesium physiology and pharmacology. Br J Anaesth 1999; 83: 302–20
5 Roscoe A, Ahmed AB. A survey of perioperative use of magnesium sulphate in adult cardiac surgery in UK. Anaesthesia 2003; 58: 363–84[Medline]
6 McKee JA, Brewer RP, Macy GE, et al. Analysis of the brain bioavailability of peripherally administered magnesium sulfate: a study in humans with acute brain injury undergoing prolonged induced hypermagnesemia. Crit Care Med 2005; 33: 661–6[Medline]
7 Lu J, Pfister M, Ferrari P, Chen G, Sheiner L. Pharmacokinetic-pharmacodynamic modelling of magnesium plasma concentration and blood pressure in preeclamptic women. Clin Pharmacokinet 2002; 41: 1105–13[CrossRef][Web of Science][Medline]
8 Lu J, Nightingale CH. Magnesium sulfate in eclampsia and pre-eclampsia. Clin Pharmacokinet 2000; 38: 305–14[CrossRef][Medline]
9 van den Bergh WM, Algra A, van Kooten F. et al. Magnesium sulfate in aneurysmal subarachnoid hemorrhage: a randomized controlled trial. Stroke 2005; 36: 1011–5
10 van Norden AG, van den Bergh WM, Rinkel GJ. Dose evaluation for long-term magnesium treatment in aneurysmal subarachnoid haemorrhage. J Clin Pharm Ther 2005; 30: 439–42[CrossRef][Medline]
11 Doufas AG, Sessler DI. Physiology and clinical relevance of induced hypothermia. Neurocrit Care 2004; 1: 489–98[Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||