2. Introduction
īŽ 4th most plentiful cation in humans (after Na, K, and Ca)
īŽ 2nd most important intracellular cation (after K)
īŽ Distribution- bones(53%), muscles(27%), soft tissues(19%) and
in serum and RBCs(less than 1%)
īŽ S. Mg â 3 forms- ionised(62%), protein bound( 33%), complexed
to anions such as citrate, PO4( 5%)
īŽ Ionised fraction is physiologically active
4. Physiological role
īŽ Physiological antagonist of Ca
īŽ Involvement of Mg in Na K ATPase- essential in maintaining
transmembrane Na and K gradients and normal K conc.
īŽ Determinant of electric potential across cell membranes
īŽ Generation of C-AMP is Mg dependant
īŽ Activation of many enzyme systems, including those involved in
energy metabolism
īŽ Essential role in production of ATP
īŽ Synthesis of DNA, RNA and protein
5. Physiological role
īŽ Direct effect on myocardium and vascular smooth muscle- depress
contractility, block catecholamine receptors, inhibits release of
catecholamines from adrenal medulla, peripheral adrenergic receptors
īŽ Blunts response of vascular tissue to vasoconstrictors
īŽ Bronchodilator, decreases PVR
īŽ Decreases release of acetylcholine at neuromuscular junction
īŽ Decreases excitability of nerves and muscles, involved in contraction
and relaxation of muscles
īŽ Suppress epileptic foci and reverse cerebral vasospasm
īŽ Tocolytic
īŽ Inhibits platelet activity, increases bleeding time
6. Mg homeostasis
īŽ Body stores regulated by hormonal and metabolic effects on
gi absorption and renal excretion
īŽ Normal levels- 0.7- 1.05mmol/l
īŽ GI absorption- ileum and colon, inversely proportional to intake
īŽ Absorbed Mg excreted primarily by kidney
īŽ Majority of reabsorption in ascending limb of Henleâs loop
īŽ Aldosterone increses renal excretion
īŽ PTH enhances gut absorption, reduces renal excretion of Mg
8. Pharmacology
īŽ 2ml, 5ml and 10 ml ampoules, clear solution for infusion
īŽ Not to be stored above 25 degrees celsius
īŽ Active substance - Magnesium sulphate heptahydrate
īŽ 2ml= 1g MgSO4= 4mmols= 8 meq= 98 milligram elemental Mg
īŽ Too rapid administration- hypotension and even asystole
īŽ Reduced dose in elderly and in renal failure- use with caution
īŽ Use with caution in Myasthenia gravis, muscular dystrophy
īŽ Contraindications- Heartblock, obstetrics- within 2 hours of delivery
īŽ Drug interactions- Digoxin , Beta blocker and CCB, NDMR
īŽ Antidote- resp depression or HB- iv calcium
hypotension- calcium/ dopamine
9. Hypomagnesemia
īŽ Plasma Conc < 0.7mmol/l
īŽ Plasma Mg is less than 1% of total body Mg
īŽ Overall deficiency may exist even with normal plasma levels
īŽ Low serum Mg generally indicates low total body Mg, exceptions-
following massive crystalloid infusion, hypoalbuminemia
īŽ Suggestions that hypomagnesemia may be the most
underdiagnosed electrolyte deficiency
īŽ Relatively common disorder
10. Hypomagnesemia - causes
īŽ Decreased intake- elderly, chronic alcoholics, pancreatic
insufficiency, short bowel syndrome, TPN with insufficient Mg
īŽ Excessive renal loss- loop diuretics, ACEI, Gentamicin, interstitial
nephritis, diuretic phase of ATN, hyperaldosteronism
īŽ Extra renal losses- prolonged diarrhoea, long term NG drainage
īŽ Redistribution- treatment of DKA with insulin dextrose, massive
transfusion with citrated blood
11. Hypomagnesemia-Clinical manifestations
īŽ CVS- HTN, Angina, Arrythmias, digoxin toxicity, ECG changes
īŽ Neuromuscular- myoclonus, cramps, stridor, Chovstekâs and
Trousseauâs signs, convulsions and coma
īŽ Psychiatric disturbances- confusion, psychosis including
Wernickeâs encephalopathy
īŽ Co existing electrolyte disturbances- hypokalemia, hypocalcemia
12. Hypomagnesemia- Treatment
īŽ Normal homeostasis of Mg requires daily intake of 10-20 mmol
īŽ Mg replacement therapy particularly important in critically ill
īŽ Emergency- 10-20 mmol in 50 ml 5% D iv over 15-30mins,
followed by 40 mmol over 4 hrs iv
īŽ Critically ill(c/c deficiency)- 40 mmol iv on day 1 and
10-20 mmols on days 2-5
īŽ Less severely ill- 15 mmols/day, NG/PO
īŽ Renal function should be adequte before Mg administration
īŽ IV administration should be stopped if hypotension/ bradycardia,
if plasma conc. > 2.5 mmol/l or if DTR disappear
13. Hypermagnesemia
īŽ Iatrogenic- overdose in treatment of preeclampsia/eclampsia
īŽ End stage renal disease
īŽ High intake of antacids and use of purgatives
īŽ Adverse effects enhanced by hypocalcimea
īŽ GI- Nausea, vomiting, diarrhoea
īŽ CVS- Prolongation of PR interval, QRS complex and QT interval,
hypotension and bradycardia, Complete HB and cardiac arrest
(10-12.5mmol/l) can also occur
īŽ CNS- Disappearance of DTR (levels> 4-5 mmol/l), depressed
respiration and apnoea due to paralysis of voluntary muscles
(5-7.5mmol/l)
Treatment-
īŽ Stop medications
īŽ iv calcium gluconate 2.5-5mmol bolus
īŽ Diuretics/ dialysis
14. PIH and Eclampsia
īŽ Major cause of maternal mortality and fetal loss
īŽ Uteroplacental ischaemia
īŽ Multisystem disorder affecting CVS, resp, hepatic, renal,
haemostatic and CNS
īŽ Control BP and abnormal haemodynamic state, prevent
convulsions, ensure safe delivery
īŽ MgSO4 is the most widely used anti convulsant
15. MgSO4 in Preeclampsia
īŽ Magpie Trial- Lancet 2002- â MgSO4 halves the risk of eclampsia
and probably reduces the risk of maternal death with no
substantive harmful effects to mother or baby in short termâ
īŽ Intense cerebral vasospasm with increased sensitivity to pressor
agents
īŽ Reduction in cerebral blood flow causing convulsions
īŽ MgSO4 in PIH- reduces intracerebral vasospasm, as measured by
Doppler examination of MCA
16. MgSO4 in Eclampsia
īŽ Collaborative Eclampsia trial ( Lancet,1995)â superiority of MgSO4
over Diazepam & Phenytoin in prevention of reccurent convulsions in
eclampsia
īŽ Reduction in incidence of eclamptic convulsions in women with PIH
īŽ Alters cardiovascular response to endotracheal intubation(40mk/kg
after induction agent, 30mg/kg in a patient on Magnesium therapy)
īŽ Less foetal depression than Alfentanil
īŽ For very severe preeclampsia- combination of MgSO4 and Alfentanil
superior to MgSO4 alone
17. MgSO4 in PIH
īŽ MgSO4 is the DOC for prevention and treatment of eclamptic
seizures
īŽ Loading dose of 4 g( some centres use 5g) iv over 5 mins
followed by iv infusion at 1-2g/hr for 24 hrs after last convulsion
īŽ If further convulsion occurs, another 2-4 g given iv over 5 mins
īŽ Therapeutic range of 2-3.5mmol/l recommended
īŽ IM route- painful, less predictable plasma concentrations
īŽ 5 g im, then 2.5g im every 4 hrs until 24 hrs after last seizure
īŽ Plasma conc of 2-4 mmol/l usually acceptable
18. MgSO4 in cardiovascular anaesthesia
īŽ Hypomagnesemia is common after CPB- Mg widely accepted in
treatment and prophylaxis of arrythmias after CPB
īŽ Anti arrythmic agent- post MI, torsades de pointes, intractable VT/
VF, digoxin induced arrythmias, multifocal atrial tachycardia
īŽ Component of some cardioplegic solutions- protects ischemic
myocardium especially during reperfusion
īŽ Aortic cross clamping- NMDA antagonsit- protection to spinal
cord during repair of supra renal anuerysms
īŽ Control of hypertensive responses to laryngoscopy and intubation-
suppress stress response at a dose of 40mg/kg
19. Mg and anaesthesia
īŽ Both hypo and hyper magnesemia- anaesthetic implications
īŽ Frequently accompanied by other electrolyte disturbances
īŽ If not urgent, postpone procedure
īŽ Increased risk of perioperative arrythmias
īŽ High chances of stridor provoked by airway stimulation, upon
induction of hypomagnesemic patients
īŽ Avoid hyperventilation, as it further lowers Mg levels
īŽ Vasodilation produced by volatile agents, narcotics may be
exacerbated by Mg leading to hypotension
20. Mg and anaesthesia
īŽ It decreases presynaptic release of acetylcholine and reduces
sensitivity of post junctional membrane
īŽ NDMR potentiated by Mg
īŽ MgSO4 causes dose related depression of acetylcholine release
īŽ Mg decreases twitch response without TOF fade, unlike NDMR
īŽ Pancuronium, rocuronium and vecuronium are potentiated by Mg
īŽ Reduced dose of muscle relaxant
īŽ Use peripheral nerve stimulator
21. Other clinical uses of Magnesium
īŽ Phaeochromocytoma crisis -bolus dose of 2-4 g followed by infusion at 1g/hr-
marked anti adrenergic effect, inhibition of release of catecholamines and calcium
channel blocking property allied to its effect on release of acetylcholine
īŽ Anaesthetic management of phaeochromocytoma resection
īŽ Asthma- bronchodilator- calcium antagonism, inhibitory action on smooth muscle
contraction, on Histamine release from mast cells and Acetylcholine release from
cholinergic nerve terminals. IgE stimulation increases calcium conc intracellularly,
leading to Histamine release
īŽ Tetanus- MgSO4 in conjunction with sedation eg: clonidine, reduce cardiovascular
(autonomic) instability and inhibits release of catecholamines, reduces spasms
īŽ Sub arachnoid haemorrhage- neuroprotective mechanisms- inhibition of release
of excitatory aminoacids, blockade of NMDA glutamate receptors, non competitive
antagonist of voltage dependant Ca channel, cerebrovascular dilatory activity
22. From the journals
īŽ MgSo4 attenuates arterial pressure increase during lap
cholecystectomy - BJA (2009)103(4)
īŽ MgSO4 as an adjuvant to intrathecal bupivacaine in mild pre
eclampsia undergoing CS- reduces post op analgesic requirements-
IJOA 2010;19
īŽ MgSO4 in severe tetanus improves muscle spasm and cardiovascular
stability- Anaesthesia 2008;63
īŽ Intra articular inj of MgSO4 enhances analgesic effect of intra
articular Bupivacaine- Anaesth Analg 2008;106
23. References
īŽ Cations- Pottasium, Calcium, Magnesium BJA CEACCP 2012 Vol 12,No 4
īŽ Magnesium: an emerging drug in anaesthesia- Editorial, BJA (2009)103(4)
īŽ Magnesium and the anaesthetist BJA CEACCP 2001,Vol 1 No 1
īŽ Magnesium- Physiology and pharmacology, BJA 1999;83:302-20
īŽ Clinical uses of Magnesium infusions in Anaesthesia,
Anaesth Analgesia 1992;74:129-136