Letters to the Editor: Letter to the Editor
To the Editor
The recent review by Pant et al.1 contains some comments related to magnesium with which we disagree. The pharmacokinetic statements are open to debate. The duration of effect is stated as 30 minutes, but studies in animals suggest a duration of effect of 9 to 10 minutes.2a These data are consistent with extensive experience regarding the use of magnesium in the management of pheochromocytoma.3 Magnesium kinetics fit a 2-compartment model: a central compartment approximating plasma volume and a peripheral compartment approximating the extracellular fluid.4–6 Consequently, a bolus injection produces a brief increase in magnesium concentration that decreases rapidly through redistribution.
The comments on data pertaining to fetal adverse effects of magnesium are based on a reference that refers to prolonged infusions using much greater doses of MgSO4 than normal (6-g loading dose and 2–3 g/h) and are not relevant to bolus injection.7 The equilibration of fetal concentrations is delayed by about 2 hours.6 This finding is confirmed in both controlled trials in which the fetal magnesium concentrations at delivery were approximately half the peak maternal level measured.8,9 Neither quoted randomized controlled trial reported adverse neonatal effects with equal or better Apgar scores in the magnesium groups compared with those seen with either lignocaine or alfentanil.8,9 However, current data are inadequate to assess the neonatal safety of any of the medications listed.
Magnesium is potentially dangerous because of its neuromuscular-blocking effects in excessive dosing. The other maternal toxic effects ascribed to magnesium derive mainly from reports of massive accidental overdose in unventilated mothers. Extremely high plasma levels up to 15.7 mmol/L have been reported but with generally favorable outcomes after appropriate rescue therapy including intubation and ventilation.10–12 The claim that tachycardia was caused by magnesium in both randomized controlled trials is incorrect. The reported tachycardia occurred after the induction of anesthesia followed by the study drug. All 3 groups showed a tachycardia that was slightly better attenuated by alfentanil than magnesium.8,9 Data in animals do not support the argument that magnesium causes tachycardia.13,14
The claimed adverse neonatal and maternal effects of magnesium in Table 1 have been transposed.
Our extensive clinical experience does not suggest adverse maternal or neonatal consequences when 30 mg/kg IV is used immediately after induction of anesthesia in magnesium-treated patients and 45 mg/kg if the patient is magnesium naive. The only consideration is the interaction of magnesium with nondepolarizing relaxants, which is easily managed by reducing the relaxant dose or using succinylcholine for cesarean section.
In our view, for reasons of availability, cost-effectiveness, and safety, magnesium remains a highly appropriate adjunct for the control of the hypertensive response to tracheal intubation in pre-eclampsia.
Mike F. James, MBChB, PhD, FRCA, FCA(SA)
Robert A. Dyer, MBChB, PhD, FCA(SA)
Department of Anaesthesia
University of Cape Town
Cape Town, South Africa
a van den Berg MM, Kellaway LA, Swanevelder J, James MF. Dose-response of magnesium sulphate-induced neuromuscular block in an in vivo rat model. Abstract presented at the South African Society of Anaesthesiologists Congress, Durban, 2015. South African Journal of Anaesthesia and Analgesia, in press.
1. Pant M, Fong R, Scavone B. Prevention of peri-induction hypertension in preeclamptic patients: a focused review. Anesth Analg. 2014;119:1350–6
2. Ludbrook GL, James MF, Upton RN. The effect of magnesium sulfate on cerebral blood flow velocity, cardiovascular variables, and arterial carbon dioxide tension in awake sheep. J Neurosurg Anesthesiol. 1999;11:96–101
3. James MF, Cronjé L. Pheochromocytoma crisis: the use of magnesium sulfate. Anesth Analg. 2004;99:680–6
4. Chuan FS, Charles BG, Boyle RK, Rasiah RL. Population pharmacokinetics of magnesium in preeclampsia. Am J Obstet Gynecol. 2001;185:593–9
5. Egelund TA, Wassil SK, Edwards EM, Linden S, Irazuzta JE. High-dose magnesium sulfate infusion protocol for status asthmaticus: a safety and pharmacokinetics cohort study. Intensive Care Med. 2013;39:117–22
6. Lu JF, Nightingale CH. Magnesium sulfate in eclampsia and pre-eclampsia: pharmacokinetic principles. Clin Pharmacokinet. 2000;38:305–14
7. Abbassi-Ghanavati M, Alexander JM, McIntire DD, Savani RC, Leveno KJ. Neonatal effects of magnesium sulfate given to the mother. Am J Perinatol. 2012;29:795–9
8. Allen RW, James MF, Uys PC. Attenuation of the pressor response to tracheal intubation in hypertensive proteinuric pregnant patients by lignocaine, alfentanil and magnesium sulphate. Br J Anaesth. 1991;66:216–23
9. Ashton WB, James MF, Janicki P, Uys PC. Attenuation of the pressor response to tracheal intubation by magnesium sulphate with and without alfentanil in hypertensive proteinuric patients undergoing caesarean section. Br J Anaesth. 1991;67:741–7
10. Morisaki H, Yamamoto S, Morita Y, Kotake Y, Ochiai R, Takeda J. Hypermagnesemia-induced cardiopulmonary arrest before induction of anesthesia for emergency cesarean section. J Clin Anesth. 2000;12:224–6
11. Fletcher SJ, Parr MJ. Life-threatening magnesium toxicity. Intensive Care Med. 2000;26:257
12. McDonnell NJ. Cardiopulmonary arrest in pregnancy: two case reports of successful outcomes in association with perimortem Caesarean delivery. Br J Anaesth. 2009;103:406–9
13. James MF, Cork RC, Dennett JE. Cardiovascular effects of magnesium sulphate in the baboon. Magnesium. 1987;6:314–24
14. Nakaigawa Y, Akazawa S, Shimizu R, Ishii R, Ikeno S, Inoue S, Yamato R. Effects of magnesium sulphate on the cardiovascular system, coronary circulation and myocardial metabolism in anaesthetized dogs. Br J Anaesth. 1997;79:363–8