MAGNESIUM

&
ANAESTHESIA
 Introduction
Magnesium…

•Is the 4th most plentiful cation in the body

•intake averages 20-30mEq/d (240-370mg/d) in adults

- Only about 30-40% is absorbed, mainly in the distal small bowel
-About 50% is sequestered in bone and is not readily exchangeable with other
compartments.
-The ECF contains only about 1% of total body Mg2+.The remainder resides in
the intracellular compartment.

•Normal plasma Mg concentration : 1.4 to 2.1 mEq/L (0.70 to 1.05 mmol/L).

•The maintenance of plasma Mg2+ concentration

-dietary intake
-effective renal and intestinal conservation.
-Within 7 days of initiation of a Mg-deficient diet, renal and stool Mg2+
excretion each fall to about 1 mEq/day (0.5 mmol/day).

•Renal excretion is the primary route of elimination

- 25% of filtered Mg2+ is reabsorbed in the proximal tubule
- 50-60% is reabsorbed in the thick ascending limb of the loop of Henle
•Factors that increase Mg2+ reabsorption in the kidneys:
-hypoMg2+
-PTH
-hypoCa2+
-ECF depletion
-metabolic alkalosis

•Factors that increase renal excretion:

-hyperMg2+
-acute volume expansion
-hyperaldosteronism
-hyperCa2+
-ketoacidosis
-diuretics
-PO4- depletion
-alcohol ingestion

•Plasma Mg2+ concentration and either total body Mg2+ or intracellular Mg2+
content are not closely related. However, severe plasma hypoMg2+ may reflect
diminished body stores of Mg2+.
•Many uses of Mg2+:
-many enzymes are Mg2+ activated or dependent.
-required by all enzymatic processes involving ATP and by
many of the enzymes involved in nucleic acid metabolism.
-required for thiamine pyrophosphate cofactor activity and
appears to stabilize the structure of macromolecules such
as DNA and RNA.
-related to Ca2+ and K+ metabolism
-Muscle relaxation may be observed at serum Mg2+
concentrations above 2.5 mmol/L

•Mg2+ preparations are usually well tolerated even when given at

large dosages.

•In healthy patients plasma concentrations in the range 2–3.5mmol/L

are considered to be safe.

•The most common side-effects are

-heat sensation, pain at the injection site,
-myocardial conduction abnormalities
-rarely, hypotension, sedation and neuromuscular
depression.
 Hypomagnesemia

•Plasma Mg2+ concentration < 1.4 mEq/L (< 0.70 mmol/L).

•Common to have associated deficiencies of other intracellular components such as K+ &

PO4-

•Causes of Hypomagnesemia

Cause Comment
Alcoholism Due to both inadequate intake and excessive renal excretion

Gl losses Chronic diabetes, Steatorrhea, Severe diarrhoea, Prolonged NG

suctioning, Small bowel bypass, Acute pancreatitis, dietary deprivation

Pregnancy-related Pre-eclampsia /eclampsia,  Lactation (increased Mg requirements)

1° renal loss Rare disorder(s), Inappropriately high urinary Mg excretion without

apparent cause (eg.Gitelman's syndrome)

2° renal losses Loop and thiazide diuretics, Hypercalcemia, After removal of

parathyroid tumor, DKA, Hypersecretion of aldosterone, thyroid
hormones or ADH, 
Nephrotoxins (amphotericin B, cisplastin, cyclosporine, aminoglycosides)

Cutaneous losses Burns, excessive sweating

 Clinical Features
•Symptomatic Mg2+ depletion is associated with refractory hypoK+(due to renal
K+ wasting), hypoCa2+(impaired PTH secretion) & metabolic alkalosis
•Facilitates development of digoxin toxicity
•Features are:
•Tremors, muscle wasting
•Positive Trousseau’s & Chvostek’s signs
•Generalised weakness, confusion, ataxia, anorexia
•Vertical nystagmus
•Tetany, seizures
•ECG
-Mild to moderate :prolongation of QT or QU intervals, bifid T waves, U
wave, supraventricular & ventricular ectopics
-Severe: PSVT, R-on-T phenomena, torsades de pointes, VT
 Torsade de pointes
•refers to VT characterized by polymorphic QRS complexes that change
in amplitude and cycle length, giving the appearance of oscillations
around the baseline.

•This rhythm is, by definition, associated with QT prolongation (QTc >

500ms) .
Normal QTc = QT/√RR interval = 0.38-0.46s

•May result from

-electrolyte disturbances (particularly hypoK+ and hypoMg2+)
-use of a variety of antiarrhythmic drugs (especially quinidine)
-phenothiazines and tricyclic antidepressants
-liquid protein diets
-intracranial events
-bradyarrhythmias, particularly third-degree AV block
-It also may occur as a congenital anomaly that most often
presents with torsade de pointes (syncope or sudden death) at a
young age.
•Rhythm strips of patients with drug (disopyramide)-induced torsade de
pointes.
•The polymorphic ventricular tachycardia is associated with very long QT
intervals.
•Polymorphic VT preceded by marked QT prolongation, often in excess of
0.60 s.
•These patients often have multiple episodes of nonsustained polymorphic VT
associated with recurrent syncope, but they also may develop VF and sudden
cardiac death.
 Therapy

•directed at removing the precipitating factors, i.e., correcting metabolic

abnormalities and removing drugs that have induced the prolonged QT
interval.

•In the setting of drug-induced torsade de pointes

-atrial or ventricular overdrive pacing
-and the administration of IV Mg2+ (8mmol as a bolus over 2-5min
followed by a 60mmol infusion over 24h)

•For patients with the congenital prolonged QT interval syndrome

-adrenergic blocking agents have been the mainstay of therapy;
-agents that shorten the QT interval may also be useful
(e.g.phenytoin).
-Pacing in combination with beta blockers and sympathectomy when
beta blockers fail, but it is not uniformly successful
-ICDs with dual chambered pacing capability and beta blockers have
become the treatment of choice for patients with recurrent
episodes despite beta blockers.
 Management
•Recommended daily allowance of Mg2+ in adults :
-350mg (14.5mmol) for men
-280mg (11.67mmol) for women
•Serum Mg2+ < 0.6mmol/L or 1.4mg/dL in isolated asymptomatic
hypoMg2+ should be treated
•Correct hypoMg2+ in patients with significant underlying cardiac or
seizure disorder, concurrent severe hypoCa2+ or hypoK+
•Treat underlying cause
•Reduce the rate of correction by 25-50% in patients with renal failure
as overzealous correction will cause hyperMg2+
Mild or Chronic HypoMg2+
-Oral elemental Mg2+ 240mg od-bd. Major side effect:
diarrhoea
-Refractory cases: K+ sparing diuretics eg. amiloride &
triamterene
-Gitelman’s syndrome & cisplatin toxicity: amiloride

Severe HypoMg2+
-IV Mg2+ comes in 49.3% 5ml solution (2.47g/5ml)
-IV MgSO4 1-2g over 15min (25-30mg/kg dilute in NS).
Then maintain similar dose given in 4-8h for a day & then over
24h again
-Monitor Mg2+, Ca2+, K+, ECG
-Administration of MgSO4 in hypoCa2+ asymptomatic pt. may
further lower the ionized Ca2+ level & thereby precipitate
tetany
-Sulphate in MgSO4 can increase urinary K+ excretion
 Anaesthetic Considerations

•Although no specific anaesthetic interactions are described, coexistent

electrolyte disturbances such as hypoK+, hypophosphataemia & hypoCa2+
are often present & should corrected prior to surgery
•Isolated hypoMg2+ should be corrected prior to elective procedures
because of its potential for causing cardiac arrhythmias
•Mg2+ appears to have intrinsic antiarrhythmic properties & possibly
cerebral protective effects such that it is increasingly being
administered prior to coming off cardiopulmonary bypass.
 Hypermagnesemia

•Plasma Mg concentration > 2.1 mEq/L (> 1.05 mmol/L).

•Causes
-renal failure (GFR <30mL/min) or
-excessive intake (Mg-containing antacids or
laxatives), or both
-iatrogenic :
MgSO4 therapy for gestational HPT
-less common:
adrenal insufficiency
hypothyroidism
rhabdomyolysis
lithium administration
 Clinical manifestation

-at >10mmol/dL(>24mg/dL):
Vasodilation, bradycardia & myocardial depression can lead to
hypotension

-at 5 to 10 mEq/L (2.5 to 5 mmol/L) :

the ECG shows prolongation of the PR interval, widening of the QRS
complex, and increased T-wave amplitude

-marked hyperMg2+ can cause respiratory arrest

-at 10 mEq/L (5.0 mmol/L) :

impairment of acetylcholine release & decrease in motor end plate
sensitivity to acetylcholine in muscle: hyporeflexia, skeletal muscle weakness

-sedation

- >12 to 15 mEq/L (6.0 to 7.5 mmol/L) :

cardiac arrest may occur
 Management

•Stop all sources of Mg2+ intake (most often antacids)

•IV 10% Ca gluconate 10 to 20 mL may reverse many of the Mg-induced changes,

including respiratory depression

•A loop diuretic along with an infusion of ½ NS in 5% dextrose enhances urinary

Mg2+ excretion.

•Diuresis with NS is generally not recommended to decrease the likelihood of

iatrogenic hypoCa2+, because the latter potentiates the effects of hyperMg2+

•Hemodialysis may be valuable in severe hypermagnesemia, because a relatively

large fraction (about 70%) of blood Mg is not protein bound and thus
ultrafilterable.

•If hemodynamic compromise occurs and hemodialysis is impractical, peritoneal

dialysis is an option.
 Anaesthetic Considerations
•Requires close monitoring of the ECG, BP & neuromuscular function
•Potentiation of the vasodilating & negative inotropic properties of
anaesthetics should be expected
•Dosages of NMBAs should be redduced by 25-50%
•CBD is required when diuretic & saline infusions are used to enhance
Mg2+ excretion
•Serial measurements of Ca2+ and Mg2+ may be useful
British Journal of Anaesthesia 97 (3): 389–92 (2006)
Intra-articular magnesium is effective for postoperative analgesia in arthroscopic
knee surgery
R. S. Bondok1 * and A. M. Abd El-Hady2
1Department of Anaesthesiology and Intensive Care and 2Department of Orthopaedic Surgery,
Ain-Shams University Hospitals, Cairo, Egypt
Accepted for publication: May 31, 2006

Background.
Several medications are commonly injected intra-articularly for postoperative analgesia after
arthroscopic knee surgery. Among the potentially efficient substances, Mg could be of particular
interest through its NMDA-receptor blocking properties.
Methods.
A total of 60 patients undergoing arthroscopic knee surgery were randomly and double-blindly
assigned to two groups to receive intra-articular injection of either 10 ml of MgSO4 (50 mg/ml)
(Group M) or 10 ml of normal saline (Group C).
Analgesic effect was evaluated by measuring pain intensity (visual analogue scale; VAS) 1, 2, 6, 8, 12,
18 and 24 h after operation and the time delay between MgSO4 or saline administration and the
first requirement of supplementary analgesic medication by the patient (diclofenac).
Results.
Intra-articular Mg administration resulted in a significant reduction in pain scores in Group M
compared with Group C 1, 2, 6 and 8 h after the end of surgery [1.7 (0.59), 2.2 (0.69), 2.8 (1.01) and
3.5 (1.10) in Group M; 8.0 (1.25), 5.9 (1.12), 4.4 (0.67) and 4.5 (1.13) in Group C, respectively].
A longer delay between intra-articular injection of the study medication and first administration of
diclofenac was observed in Group M [667 (198) min] as compared with Group C [49 (13) min]. Total
diclofenac consumption was significantly lower in Group M [37.5 (38.14) mg] than in Group C [117.5
(46.95) mg]. No early side-effects were noted.
Conclusion.
Intra-articular Mg is effective for postoperative analgesia in arthroscopic knee surgery.
British Journal of Anaesthesia 2006 96(4):444-449;
Magnesium moderately decreases remifentanil dosage required for pain management
after cardiac surgery
B. Steinlechner1,*, M. Dworschak1, B. Birkenberg1, G. Grubhofer1, M. Weigl2, A. Schiferer1, T. Lang1 and A. Rajek1
1Division of Cardiothoracic and Vascular Anaesthesia and Intensive Care, University Hospital Vienna Austria
2Division of General Anaesthesia and Intensive Care, University Hospital Vienna Austria
Accepted for publication January 18, 2006.
Background.
Mg2+ is a Ca2+and an NMDA-receptor antagonist and can modify important mechanisms of
nociception. We evaluated the co-analgesic effect of Mg2+ in the postoperative setting after on-
pump cardiac surgery.

Methods.
40 patients randomly received either magnesium gluconate as an i.v. bolus of 0.21 mmol kg–1 (86.5 mg
kg–1) followed by a continuous infusion of 0.03 mmol–1 kg–1 h–1 (13.8 mg kg–1 h–1) or placebo for 12 h
after tracheal extubation. After surgery, remifentanil was decreased to 0.05 µg kg–1 min–1 and
titrated according to a pain intensity score (PIS, range 1–6) in the intubated, awake patient and a
VAS scale (range 1–100) after extubation. If PIS was 3 or VAS 30, the infusion was increased by
0.01 µg kg–1 min–1; if ventilatory frequency was 10 min–1 it was decreased by the same magnitude.

Results.
Mg2+ lowered the cumulative remifentanil requirement after surgery (P<0.05). PIS 3 was more
frequent in the placebo group (P<0.05). Despite increased remifentanil demand, VAS scores were also
higher in the placebo group at 8 (2 vs 8) and 9 h after extubation (2 vs 7) (P<0.05). Dose reductions
attributable to a ventilatory frequency 10 min–1 occurred more often in the Mg2+ group (17 vs 6;
P<0.05). However, time to tracheal extubation was not prolonged.

Conclusions.
Magnesium gluconate moderately reduced the remifentanil consumption without serious side-effects.
The opioid-sparing effect of Mg2+ may be greater at higher pain intensities and with increased
dosages.
British Journal of Anaesthesia. 89(4):594-598, October 2002.
Evaluation of effects of magnesium sulphate in reducing intraoperative
anaesthetic requirements.
Telci, L. 1; Esen, F. 1,*; Akcora, D. 1; Erden, T. 1; Canbolat, A. T. 2; Akpir, K. 1

Background
The present randomized, placebo-controlled, double-blind study was designed to assess the effect
of peroperatively administered i.v. magnesium sulphate on anaesthetic and analgesic requirements
during total i.v. anaesthesia.

Methods
81 patients (36 women, 45 men) undergoing elective spinal surgery were included in one of two
parallel groups. The Mg2+ group received magnesium sulphate 30 mg/kg as a bolus before induction
of anaesthesia and 10 mg/kg/h by continuous i.v. infusion during the operation period. The same
volume of isotonic solution was administered to the control group. Anaesthesia was maintained with
propofol (administered according to the bispectral index) and remifentanil (adjusted according to
heart rate and arterial blood pressure) infusions.

Results
A significant reduction in hourly propofol consumption was observed with Mg2+ administration. For
example, the mean infusion rate of propofol in the second hour of the operation was 7.09 mg/kg/h
in the control group vs 4.35 mg kg/h in the Mg2+ group (P<0.001). The Mg2+ group required
significantly less remifentanil (P<0.001) and vecuronium (P<0.001). No side-effects were observed
with Mg2+ administration.

Conclusion
The administration of Mg2+ led to a significant reduction in the requirements for anaesthetic drugs
during total i.v. anaesthesia with propofol, remifentanil and vecuronium.
Paediatric Anaesthesia. 13(1):43-47, January 2003.
The use of magnesium to prevent laryngospasm after tonsillectomy and adenoidectomy: a preliminary
study.
GULHAS, NURCIN MD; DURMUS, MAHMUT MD; DEMIRBILEK, SEMRA MD; TOGAL, TURKAN MD; OZTURK, ERDOGAN MD; ERSOY, M. OZCAN MD

Background
Laryngospasm is the most common cause of upper airway obstruction after tracheal extubation. Mg2+ has a
central nervous system depressant property, which contributes to the depth of anaesthesia. It also has
Ca2+ antagonist properties, which provide muscle relaxation. In this study, we aimed to determine the
effect of Mg2+ on preventing laryngospasm.

Methods
After approval of the Ethics Committee and informed parental consent, 40 patients, ASA I-II, aged 3-12
years, who were scheduled for tonsillectomy or/and adenoidectomy, were randomly divided into 2 groups.
Anaesthesia was induced with sevoflurane, lidocaine 1 mg/kg, alfentanil 10 mcg/kg, vecuronium 0.1 mg/kg &
maintained with sevoflurane 2% and 60% nitrous oxide in oxygen. After intubation, patients in group I
received 15 mg/kg Mg2+ in 30 ml 0.9% NaCl over 20 min. Patients in group II received 0.9% NaCl alone in
the same volume. After reversal of neuromuscular blockade, all patients were extubated at a very deep
plane of anaesthesia. The incidence of laryngospasm was determined until the time of discharge from the
postanaesthesia care unit.

Results
Although laryngospasm was not observed in group I, it was observed in five patients in group II (25%).
The incidence of laryngospasm in group II was significantly higher than group I. The plasma Mg2+
concentrations were significantly higher in group I than group II.

Conclusions
We found a significant decrease in the incidence of laryngospasm in paediatric patients receiving Mg2+.
It is suggested that the use of intravenous Mg2+ intraoperatively may prevent laryngospasm.
 Summary
•Mg2+ is an important intracellular cation that functions as a
cofactor in many enzyme pathways
•HypoMg2+ is a common & frequently overlooked problem,
particularly in ill patients. Associated deficiencies of other
intracellular components such as K+ & phosphorus are common
•Mg2+ affects the activity of neurones, of myocardial &
skeletal muscle fibres & of the myocardial conduction system.
It also effects vasomotor tone & hormone receptor binding
 N-methyl-D-aspartate (NMDA) receptors

•Play a major role in central nociceptive transmission, modulation and sensitization of

acute pain states

•In addition to their central location, recent studies identified NMDA receptors
peripherally in the skin, muscles and knee joints, and found that they play a role in
sensory transmission of noxious signals.

•In its inactive state, the NMDA receptor is blocked by the presence of a centrally
positioned Mg ion. Mg2+ exerts a non-competitive voltage-dependent block of the
NMDA receptor-operated ion channel, which prevents extracellular Ca2+ from
entering the cell. Afferent activity in nociceptor fibres dislodges the central Mg ion
from the NMDA receptor, therefore allowing Ca2+ influx into the cell.
•Mg2+ can be considered as a physiological blocker of NMDA receptors.
Mg2+ not only blocks the NMDA channel in a voltage-dependent manner but
also potentiates NMDA-induced responses at positive membrane potentials.

•More recently, it has been demonstrated to reduce postoperative analgesic

requirements. The mechanism of peripheral antinociceptive effect of NMDA
antagonism has not been precisely defined. It has been hypothesized to
occur through an analgesic and antiinflammatory effect.

•NMDA antagonists reduce the excitability of nociceptive input terminals of

C-fibres, which play a role in the central processing of pain.

•The anti-inflammatory action in the peripheral tissues occurs through

antagonizing the release of inflammatory mediators such as histamine,
cytokines and serotonin, which in turn excite nociceptors.
NMDA Receptor
Legend:
1. Cell membrane
2. Channel blocked by Mg2+ at
the block site (3)
3. Block site by Mg2+
4. Hallucinogen compounds
binding site
5. Binding site for Z2+
6. Binding site for
agonists(glutamate) and/or
antagonist ligands
7. Glycosilation sites
8. Proton biding sites
9. Glycine binding sites
10. Polyamines binding site
11. Extracellular space
12. Intracellular space