Download Slide 1

ROLE OF MAGNESIUM
IN CRITICAL CARE
Dr.May Mostafa Darwish
Assistant lecturer of Anesthesia and ICU
Ain Shams University
INTRODUCTION
 Magnesium is essential for human life:
 It plays a fundamental role in many cellular functions,
such as storage, metabolism, and energy utilization.
 Mg ions are involved as a cofactor in :
 many enzymatic reactions
 hormone receptor binding
 protein synthesis
 neuromuscular function
 and nucleic acid stability
 4th most common mineral salt
(P/Ca/K/Mg.)
 2nd intracellular cation after
potassium
 4th plasma cation
(Na/K/Ca/Mg…)
 53% in bone, 27% in muscle,
19% in soft tissues, 0.5% in
erythrocytes, 0.3% in serum
In serum:
Ionized (active form): 60%
Protein-bound: 33%
In anion complexes (phosphates and citrates): 7%
ionized
protein
bound
anion
complexes
 Normal plasma Mg 2+ concentration :
1.7 to 2.4 mEq/L (0.70 to 1.0 mmol/L)
 Daily recommended requirement:
250-350 mg (10.4–14.6 mmol) in adults
 Cocoa powder, chocolate, nuts, leafy green
vegetables, cereals, seafood are rich
sources for Mg2+
 The maintenance of plasma Magnesium
concentration through:
• dietary intake .
• effective renal and intestinal
conservation.
 Renal excretion is the
primary route of
elimination
•
25% is reabsorbed in the
PCT.
•
50-60% is reabsorbed in
the thick ascending limb of
the loop of Henle.
Mg absorption and cellular uptake:
PTH : intestinal absorption↑
Vitamin D: intestinal absorption↑
Insulin: cellular uptake↑
Glucagon: renal reabsorption ↑
Actions of Magnesium
1. Endogenous calcium antagonist by affecting
its uptake and distribution.
2. Modulator of Na+ and K+ currents, thus
influencing membrane potential.
3. Depressant effects in CNS :
 antagonist of the (NMDA) receptor
 inhibitor of catecholamine release.
What is the
role of
magnesium
in ICU??
Magnesium and
Cardioprotection
I. Acute myocardial infarction.
 Coronary and systemic VD :
 improve metabolism of cardiomyocytes
 attenuate ischemia–reperfusion injury of myocardial
tissue.
 Decreases myocardial membrane excitability:
 Na+/K+ ATPase and Ca2+ ATPase are important
regulators of myocardial membrane stability.
 Attenuates the incidence of infarction-related
arrythmias:
 prolongs the ARP and shortens the RRP
II. Cardiac Arrythmias
:
 slows electrical activity of the SAN.
 prolongs AV conductance.
 increases the refractory period of the
AVN.
 Types :
1. AF and ventricular arrhythmias after cardiac
and thoracic surgery
2. digoxin induced supraventricular and
ventricular arrhythmias
3. multifocal atrial tachycardia
4. polymorphic ventricular tachycardia
(Torsade de points)
5. VF from drug overdoses.
III. Pulmonary
Hypertension:

PH is defined as a mean PA pressure
greater than 25 mmHg at rest and > 30
mmHg during exercise.

Magnesium is a potent vasodilator and
hence has the potential to reduce the high
pulmonary arterial pressures associated with
persistent pulmonary hypertension (PPHN)
Magnesium and
Preeclampsia
Eclampsia and Preeclampsia
 Systemic, cerebral, and uterine vasodilation
by:
1) Increase concentrations of the two endogenous
potent vasodilators
 endothelium-derived relaxing factor and
 calcitonin gene-related peptide
2) It attenuates the circulating concentrations of
endothelin-1 (an endogenous vasoconstrictor)
 Dose : loading 4–6 g /20–30 min & maintenance
of 1–2 g/h.
 The infusion should be continued for at least 24 h
after delivery.
 To avoid serious adverse effects, respiration, the
presence of tendon reflexes, and urine output
should be closely monitored.
 antenatal administration may be considered
because of its neuroprotective effects in preterm
neonates.
Magnesium and Asthma
 MgSO4 has been administered to patients to treat
acute severe asthma when conventional therapy with
oxygen, corticosteroids and continuous aerosol beta
agonists fail to provide adequate relief
 Magnesium-induced bronchodilation may be
mediated by several pathways:
1.
attenuation of calcium-induced muscle contractions
2.
inhibition of cholinergic neuromuscular
transmission
3.
antiinflammatory activity
4.
potentiation of β-agonists on adenylyl cyclase
5.
reversal of magnesium depletion after β-adrenergic
treatment
 IV MgSO4 provides additional benefit in
moderate to severe acute asthma in patients
treated with bronchodilators and steroids.
 Nebulised inhaled MgSO4 in addition to beta2agonist used in ttt of acute asthma exacerbation
improves pulmonary function.
 Mg also possesses mild sedative effects valuable
to achieving anxiolysis and relaxation in acute
bronchospasm.
Magnesium and
Neuroprotection
 Mg was shown to protect neurons and
glia cells by:
1) inhibiting ischemia-induced glutamate
release
2) inhibiting calcium-dependent enzymes
 Therefore Mg exertes antiexcitotoxic
properties and preventes cellular
apoptosis.
I. Stroke:
 The most promising time frame to facilitate
maximal Neuroprotection is assumed to cover
the first 3 h after onset of ischemia.
II. Subarachnoid Hemorrhage:
 Delayed cerebral ischemia is one of the main
causes of death and disability after SAH and
usually occurs 4–10 days after the initial
bleeding event.
 IV MgSO4 as an adjuvant to nimodipine may
reduce delayed cerebral ischemia by 34%
III. Carotid Surgery:
 Patients undergoing
carotid endarterectomy
are at particular risk for
postoperative cognitive
deficits caused by cortical
ischemia after
intraoperative
hypotension or embolic
events.
 Mg is known to improve
neurocognitive function
on 1st postoperative day
IV. Spinal Cord Injury:
 Once 1ry injury to the
spinal cord has occurred,
reduction of 2ry injury and
ongoing ischemia by
stabilizing hemodynamics
and spinal perfusion
pressure is most
important.
 Mg has proven its
neuroprotective potential
in spinal cord injury.
Magnesium and
Pheochromocytoma
 Pheochromocytoma is a CA producing and
secreting neoplasm arising 1ry from the
adrenal medulla.
 Surgical removal of Pheochromocytoma
possesses significant challenge dt the
hemodynamic disturbances occurring when a
tumor is manipulated and finally resected.
 Standard preoperative treatment includes
pharmacologic stabilization by  and β
adrenergic antagonists.
 Magnesium may stabilize hemodynamics :
1. inhibition of CA release from the adrenal
medulla and peripheral adrenergic nerve
endings.
2. direct blockade of CA receptors.
3. antiarrhythmic properties related to calcium
channel antagonism.
 An initial bolus dose of 40-60mg/kg IV followed
by 2g/hr has been a suggested regimen
Pheochromocytoma Crisis
 Mg was shown to improve severe hypertension and
hypertensive encephalopathy in patients with
pheochromocytoma crisis.
 Based on arteriolar -dilating properties, its use might
be advantageous to that of sodium nitroprusside,
which dilates both arterioles and venules and may
thus worsen hemodynamics, especially in
hypovolemic patients.
 Because Mg was shown to inhibit CA receptors, it
may be superior to other competitive adrenergic
antagonists, such as phentolamine because excessive
CA concentrations may be present.
Magnesium and Tetanus
 Mg reduces spasms and autonomic
instability in tetanus.
 A proposed regimen for management of
tetanus is 5g MgSO4 IV over 20mins
followed by 2g/hour IV infusion.
 This can be increased by 0.5g/hour
until there is relief of spasms or loss of
patellar reflexes.
Magnesium and
Analgesia
 Several studies report antinociceptive effects
of Mg when administered IV or intrathecally.
 Suggested mechanisms include the inhibition
of calcium influx (CCB augment morphineinduced analgesia and decrease total opioid
consumption ) and antagonism of NMDA
receptors
 In addition, Mg seems to attenuate or even
prevent central sensitization after peripheral
tissue injury or inflammation because of
inhibition of dorsal horn NMDA receptors.
Magnesium
and
Shivering
 Hypothermia may be an effective ttt for
stroke or acute MI ; however, it provokes
vigorous shivering, which causes potentially
dangerous hemodynamic responses and
prevents further hypothermia.
 Mg is an attractive anti-shivering agent
because it reduces the threshold (triggering
core temperature) and gain of shivering
without substantial sedation or muscle
weakness.
Magnesium and
Laryngoscopic Intubation
Response
 The role of Mg in blunting the intubation
response is evolving:
 It has direct VD properties on coronary arteries
and inhibiting CA release, thus attenuating the
hemodynamic effects during endotracheal
intubation.
 Beside its role in blunting the pressor response to
intubation , it also produces less ST changes in
coronary artery disease pts.
 It was also concluded that pretreatment with
different doses of Mg is more effective than
pretreatment with Lidocaine.
Magnesium and Insulin
Resistance
 Clinical situations in which glycemia remains
elevated despite increased insulin doses are frequent
in ICU.
 Mg regulates cellular glucose metabolism directly
because it serves as an important cofactor for various
enzymes and acts as a 2nd messenger for insulin.
 Furthermore, hypomagnesaemia may induce :
1. altered cellular glucose transport
2. reduced pancreatic insulin secretion
3. defective post-receptor insulin signalling
4. altered insulin– insulin receptor interactions and
thus aggravate insulin resistance
In a Nutshell
 Mg is a cost effective, widely used drug with
multidisciplinary applications.
 Majority of its physiological effects are
attributed to its calcium channel blocking
properties.
It is used as :
1.
2.
3.
4.
5.
Vasdilator (antihypertensive)
Bronchodilator
Antiarrythmic
Antiseizures
Analgesic