21891659-Magnesium-Anaesthesia

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MAGNESIUM & ANAESTHESIA

Magnesium—Essentials for Anesthesiologists: 

Magnesium—Essentials for Anesthesiologists Anesthesiology, V 114 • No 4 April 2011 REVIEW ARTICLE The current review aims to summarize the current knowledge on the physiology and pathophysiology of magnesium and on the proposed indications and recommendations for its use in different clinical settings. Using MEDLINE, the Cochrane Library, and Clinical- Trials.gov, a search was performed for studies addressing experimental and clinical effects of magnesium. Key words entered were: magnesium, physiology, toxicity, anesthesia, analgesia, pheochromocytoma, preeclampsia and eclampsia, asthma, myocardial infarction, cardiac arrhythmias, stroke, and neuroprotection.

The therapeutic use of magnesium in anesthesiology, intensive care and emergency medicine: a review: 

The therapeutic use of magnesium in anesthesiology, intensive care and emergency medicine: a review Authors: Laurent Dubé MD, Jean-Claude Granry MD PhD Journal: CAN J ANESTH 2003 / 50: 7 / pp 732–746 From the Department of Anesthesiology, University Hospital, Angers, France. References were obtained from Medline® (1995 to 2002). All categories of articles (clinical trials, reviews, or metaanalyses) on this topic were selected. The key words used were magnesium, anesthesia, analgesia, emergency medicine, intensive care, surgery, physiology, pharmacology, eclampsia, pheochromocytoma, asthma, and acute myocardial infarction.

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Magnesium is the fourth most abundant essential ion in the human body and plays a fundamental role in many cellular functions, such as storage, metabolism, and energy utilization. It serves as a cofactor for various biologic processes, including protein synthesis, neuromuscular function, and nucleic acid stability. Magnesium is an intrinsic component of many adenosine 5′-triphosphatases and an endogenous regulator of several electrolytes. Being a noncompetitive inhibitor of inositol triphosphate-gated calcium channels, magnesium functions as an endogenous calcium antagonist by affecting its uptake and distribution. Magnesium also shows modulatory effects on sodium and potassium currents, thus influencing membrane potential. In the central nervous system, magnesium exerts depressant effects, acting as an antagonist at the N -methyl-d-aspartate (NMDA) glutamate receptor and an inhibitor of catecholamine release

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A human adult body contains an average of 24 g (1 mol) magnesium, stored mainly in bone (60%) and the intracellular compartments of muscle (20%) and soft tissues (20%), primarily bound to chelators, such as adenosine 5-triphosphate and DNA. Two to three percent of intracellular magnesium is ionized and regulates intracellular magnesium homeostasis. The extracellular space comprises only1%of total body magnesium, including 0.3% found in plasma. Plasma magnesium is ionized (60%), complexed to anions (7%), or protein-bound (33%), with normal concentrations of total plasma magnesium ranging from 0.7 to 1.0 mM (1.7–2.4 mg/dl).

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Magnesium… 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 : 1.7 to 2.4 mEq/L (0.70 to 1.0 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

Administration of Mg : 

Administration of Mg Mg can be administered orally or intravenously. Intramuscular injection is also possible but painful. Oral administration of a daily dose of more than 50 mmol can cause vomiting and diarrhea. In anesthesia and intensive care, the preferred administration route is iv. Two injectable forms of Mg are available, namely Mg chloride and sulfate. Ten millilitres of a 10% Mg chloride (MgCl2) solution provide 1 g of Mg salts (= 118 mg Mg = 9 mEq = 4.5 mmol ), and 10 mL of a 10% Mg sulfate (MgSO4) solution provide 1 g of Mg salts (= 98 mg Mg = 8.12 mEq = 4.06 mmol )

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Posology differs according to indications, and several dosage recommendations have been proposed. To correct a Mg deficit, the objective is to restore normal serum concentrations, in which case slow infusion of up to 10 g/day. For its pharmacological properties, more rapid infusion is often necessary to obtain the high plasma concentrations desired. The recommended procedure is rapid infusion of 1 to 2 g of MgSO4 iv over a ten-minute period followed by continuous iv infusion of 0.5 to 1 g·hr–1 (reduced to 0.25 g·hr–1 for patients with renal insufficiency). Administration is performed under continuous electrocardiographic control, and serum concentrations of Mg or ionized Mg are determined every six hours. If Mg is given too quickly, flushing can occur, and bradycardia, cardiac arrhythmia, or cardiac arrest have been reported. There is also the increased risk of the toxic effects of Mg resulting in renal impairment

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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+.

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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.

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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

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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

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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.

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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.

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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.

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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+

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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

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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.

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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

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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

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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.

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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

Magnesium and Anesthesia: 

Magnesium and Anesthesia Magnesium has been suggested for reducing anesthetic requirements, attenuating cardiovascular effects from laryngoscopy and intubation, and exerting muscle- relaxing effects. Details of the mechanisms underlying the anesthesia-enhancing effects of magnesium remain unknown. A competitive antagonism on hippocampal presynaptic calcium channels that regulate neurotransmitter release in the central nervous system has been suggested.

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In terms of neuromuscular blockade, the inhibition of calcium-mediated release of acetylcholine from the presynaptic nerve terminal at the neuromuscular junction plays an important role. A decrease of postsynaptic sensitivity to acetylcholine and direct effects on the membrane potential of myocytes also may contribute.

Clinical Data: 

Clinical Data Two double-blind, randomized, and controlled trials demonstrated a reduction of propofol requirements guided by Bispectral Index monitoring after administration of intravenous MgSO 4 (bolus of 30 mg/kg, followed by continuous infusion of 10 mg · kg −1 · h −1 until end of surgery) in patients undergoing spinal surgery. Moreover, catecholamine release and cardiovascular effects in response to tracheal intubation were found to be attenuated by intravenous magnesium in most clinical trials.

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In a comparative study, patients received thiopental and succinylcholine with or without Mg sulfate 60 mg·kg–1 at anesthesia induction. Patients treated with Mg showed a lower increase of heart rate and systolic blood pressure after intubation. Plasma concentrations of epinephrine and norepinephrine were markedly lower after intubation in the Mg-treated group Ashton et al. found no increase in arterial pressure or heart rate and a moderate decrease of plasma catecholamine concentrations after intubation in a group treated with Mg alone before intubation

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Durmus et al. observed an increased minimal alveolar concentration of sevoflurane at the time of skin incision when magnesium was administered before anesthesia induction A similar reduction in requirements as shown for anesthetic agents was described for muscle relaxants when magnesium also was administered.

Magnesium and Analgesia : 

Magnesium and Analgesia Several animal and human studies report antinociceptive effects of magnesium when administered intravenously or intrathecally. Suggested mechanisms underlying these antinociceptive effects include the inhibition of calcium influx (calcium channel blockers augment morphine-induced analgesia and decrease total opioid consumption), antagonism of NMDA receptors, and the prevention of enhanced ligand-induced NMDA signaling in a state of hypomagnesemia. In addition, magnesium seems to attenuate or even prevent central sensitization after peripheral tissue injury or inflammation because of inhibition of dorsal horn NMDA receptors.

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Table 3 Copyright © 2011 Anesthesiology. Published by Lippincott Williams & Wilkins. 32

Table 3: 

Table 3 Table 3. Continued Copyright © 2011 Anesthesiology. Published by Lippincott Williams & Wilkins. 33

Magnesium and Obstetrics : 

Magnesium and Obstetrics Preeclampsia Preeclampsia is defined as new-onset hypertension and proteinuria developing after the 20th week of gestation up to several weeks after delivery, and it may be aggravated by seizures or coma (eclampsia). Underlying mechanisms include an abnormal vascular response to placentation with increased systemic vascular resistance, enhanced platelet aggregation, stimulation of inflammation and coagulation, and endothelial dysfunction

Mechanisms of Action : 

Mechanisms of Action Magnesium seems to improve clinical symptoms of preeclampsia and eclampsia primarily by systemic, cerebral, and uterine vasodilation. In addition to having a direct effect on the vessels, magnesium was shown to increase concentrations of the two endogenous potent vasodilators endothelium-derived relaxing factor and calcitonin gene-related peptide and attenuate circulating concentrations of endothelin-1, an endogenous vasoconstrictor

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As recommended, MgSO 4 should be applied intravenously, using a loading dose of 4–6 g over 20–30 min and a subsequent maintenance dose 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 during treatment. There is no evidence supporting the use of magnesium for tocolysis in women at risk for preterm birth. However, antenatal administration may be considered because there is Level A Evidence (AHA) showing its neuroprotective effects in preterm neonates.

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When Mg was used for tocolysis, adverse effects (flushing and headache) were more frequent with high (5 g·hr–1) than with low doses (2 g·hr–1), and Pulmonary edema occurred in two patients in the highdose group vs none in the low-dose group Mg administered to the mother may have a neuroprotective effect for the newborn. Neonatal morbidity was lower and an Apgar score below 7 at one minute was significantly less frequent in infants of mothers treated by Mg as compared to diazepam.

Magnesium and Pheochromocytoma : 

Magnesium and Pheochromocytoma Pheochromocytoma is a catecholamine-producing and secreting neoplasm arising primarily from the adrenal medulla with an estimated incidence of 500–1,100 cases in the United States each year Surgical removal of pheochromocytoma poses a significant anesthetic challenge because of the well-described hemodynamic disturbances occurring when a tumor is manipulated and finally resected. Standard preoperative treatment includes pharmacologic stabilization by α- and β- adrenergic antagonists. Several case reports have described the successful use of magnesium during pheochromocytoma crisis.

Mechanisms of Action : 

Mechanisms of Action Magnesium may stabilize hemodynamics by inhibition of catecholamine release from the adrenal medulla and peripheral adrenergic nerve endings, direct blockade of catecholamine receptors and vasodilation, and antiarrhythmic properties related to L-type calcium channel antagonism.

Clinical Data: 

Clinical Data B ecause of the tumor's low incidence, large prospective clinical trials are missing, and conclusions have to be drawn from a few small studies and case reports. In 1989, James published a series of 16 patients undergoing elective pheochromocytoma surgery, who had been given α- and β-adrenergic antagonists before surgery and received a loading dose of MgSO 4 (40–60 mg/kg), followed by a continuous perioperative infusion of 2 g/h. Additional boli of 20 mg/kg were used to keep blood pressure within ± 30 mmHg of baseline values. A total of 8–18 g MgSO 4 was administered during surgery (60–150 min). In 11 of 16 patients, magnesium was highly effective in providing hemodynamic stability, although 4 patients required additional sodium nitroprusside during manipulation of the tumor.

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The patient for whom hemodynamic control could not be obtained had a serum Mg concentration (1.3 mmol·L–1) below desired values, which may have been responsible for clinical failure. Serum Mg concentrations were high in the other patients (2–4 mmol·L–1), corresponding to inputs of 8 to 18 g of Mg in a period of 60 to 150 min. With such high doses and serum concentrations of Mg, the effects of curares were increased and it was necessary to counteract these at the end of the operation, before extubation

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Pheochromocytoma Crisis Hypertensive crisis caused by pheochromocytoma may be an additional indication for magnesium. Magnesium was shown to improve severe hypertension and hypertensive encephalopathy in three patients with pheochromocytoma. Based on magnesium's 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 magnesium was shown to inhibit catecholamine receptors, it may be superior to other competitive adrenergic antagonists, such as phentolamine and doxazosin, because excessive catecholamine concentrations may be present.

Magnesium and Asthma or Chronic Obstructive Pulmonary Disease : 

Magnesium and Asthma or Chronic Obstructive Pulmonary Disease Asthma Asthma is a common disorder affecting more than 12 million people in the United States, Mechanisms of Action. Magnesium-induced bronchodilation may be mediated by several pathways: attenuation of calcium-induced muscle contractions, inhibition of cholinergic neuromuscular transmission, antiinflammatory activity, potentiation of β-agonists on adenylyl cyclase, and reversal of magnesium depletion after β-adrenergic treatment. Evidence also exists that prostaglandin- mediated vascular smooth muscle relaxation may be magnesium-dependent, and magnesium possesses mild sedative effects that are valuable to achieving anxiolysis and relaxation in acute bronchoconstriction.

Clinical Data : 

Clinical Data Intravenous Magnesium. In 2000, a Cochrane systematic review evaluated seven trials (five adult, two pediatric) with a total of 665 patients for the efficacy of intravenous magnesium as an adjunct to standard therapy (β-agonists and systemic corticosteroids) in the treatment of severe asthma. The authors concluded that there is no evidence for the routine use of intravenous magnesium in all asthmatic patients but that it appears beneficial in patients presenting with acute severe asthma. Magnesium seems less beneficial in chronic stable asthma. A daily dose of 450 mg magnesium chelate did not benefit chronic asthmatic adults. Despite the lack of effect in chronic asthma, magnesium may be advantageous in patients with bronchial hyperreactivity.

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Inhaled Magnesium. A Cochrane review including six trials (three adult, two pediatric, one mixed) and a total of 296 patients failed to provide convincing evidence that the addition of nebulized MgSO 4 (95–385 mg or 250–280 mmol) to standard bronchodilator therapy (inhaled β-agonists) improves the outcome of patients presenting with acute asthma. Compared with β-agonist treatment alone, pulmonary function was improved, and those with severe asthma had a significant difference when analyzed separately; however, there was considerable between-study heterogeneity. The total MgSO 4 dose applied varied, dependent on the number of nebulizations and cointerventions, such as additional administration of corticosteroids, which further impairs comparisons between studies. Inhaled MgSO 4 alone did not have any benefit on pulmonary function compared with β-agonists and did not influence the rate of hospital admission.

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Chronic Obstructive Pulmonary Disease Only a small number of studies addressed the effects of magnesium on chronic obstructive pulmonary disease. In a randomized, placebo-controlled, double-blind clinical trial, Skorodin et al. studied the effects of intravenous MgSO 4 (1.2 g) after nebulized albuterol treatment in 72 patients presenting with acute exacerbation of chronic obstructive pulmonary disease. After 30–40 min, the peak expiratory flow rate was significantly improved in the magnesium group, although there was no difference with regard to dyspnea. Administration of intravenous MgSO 4 (2 g) in 22 patients with stable chronic obstructive pulmonary disease was associated with a reduction of lung hyperinflation and improved muscle strength.

Summary: 

Summary In the absence of straightforward evidence, one can rely on the 2008 revised National Asthma Education and Prevention Program guidelines for managing exacerbations of asthma. In patients with life-threatening exacerbations of asthma and in those in whom exacerbations remain in the severe category after 1 h of intensive conventional therapy, the administration of magnesium sulfate can be considered (Class II, Level of Evidence A, AHA). It is also suggested that nebulized salbutamol be administered in isotonic MgSO 4 because it provides greater benefit than when delivered in normal saline. There is little evidence to recommend the routine use of magnesium in patients with chronic obstructive pulmonary disease.

Magnesium and Neuroprotection : 

Magnesium and Neuroprotection Because of its diverse roles in various cellular functions, magnesium has been suggested to have beneficial effects in several neurologic disorders. Mechanisms of Action In addition to NMDA antagonism and especially important for the ischemic penumbra, magnesium was shown to protect neurons and glia cells by numerous other modes of action. By inhibiting ischemia-induced glutamate release and calcium-dependent enzymes, magnesium exerted antiexcitotoxic properties in different animal models and prevented cellular apoptosis in hippocampal slices of newborn piglets.

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In a rat model of cerebral ischemia, cortical spreading depression and anoxic depolarization were shown to be attenuated. Of particular interest in subarachnoid hemorrhage, magnesium is a cerebral vasodilator, shown to increase blood flow in rat brain, as desired

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Mg administered to the mother may have a neuroprotective effect for the newborn. Neonatal morbidity was lower and an Apgar score below 7 at one minute was significantly less frequent in infants of mothers treated by Mg as compared to diazepam. The multicentre study referred to above found a decrease in neonatal morbidity when Mg was used at the doses administered for eclampsia (loading dose of 4 g iv followed by an infusion of 1 g·hr–1 or im administration of 5 g every four hours). In a population of low birth weight infants, maternal treatment with Mg before delivery was associated with a reduced risk of cerebral palsy and a decrease of ultrasonographically detected lesions of cystic periventricular leukomalacia.

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This neuroprotective effect of Mg in premature infants was not found in other studies. The discrepancies in the results of these retrospective studies led several researchers to undertake prospective studies. One of these investigations was discontinued early because of a significant increase in the deaths of newborns whose mothers had been given Mg at tocolytic doses (loading dose of 4 g followed by infusion of 2–3 g·hr–1). A correlation seemed likely between high ionized Mg concentrations in cord blood and death and the deaths occurring in the Mg group were often attributable to marked prematurity

Stroke : 

Stroke Field Administration of Stroke Therapy—Magnesium (FAST-MAG) Trial, currently is evaluating the benefit of field-initiated (within the first 2 h after onset of symptoms) magnesium in improving long-term functional outcome of patients with cerebral infarction and intracerebral hemorrhage. Trial demonstrated dramatic early recovery in 42% of patients and good 90-day global functional outcome in 75% of patients treated with intravenous MgSO 4 (4-g loading dose followed by 16 g as maintenance dose) within 2 h after stroke onset Although there is little evidence for a time frame facilitating maximal neuroprotective efficacy of magnesium in stroke, the most promising window is assumed to cover the first 3 h after onset of ischemia.

Carotid Surgery : 

Carotid Surgery Patients undergoing carotid endarterectomy are at particular risk for postoperative cognitive deficits caused by cortical ischemia after intraoperative hypotension or embolic events. A single trial analyzed 92 patients with asymptomatic or symptomatic carotid artery stenosis with ≥60% scheduled for carotid endarterectomy. MgSO 4 given as a 2-g loading dose over 25 min and a maintenance dose of either 8 g or 16 g over 24 h significantly improved neurocognitive function on postoperative day 1 compared with placebo or higher-dose MgSO 4 (4-g loading dose, 16 g as maintenance dose).

Subarachnoid Hemorrhage : 

Subarachnoid Hemorrhage Delayed cerebral ischemia is one of the main causes of death and disability after subarachnoid hemorrhage and usually occurs 4–10 days after the initial bleeding event. The placebo-controlled Magnesium Sulfate in Aneurysmal Subarachnoid Hemorrhage (MASH) Trial suggested that intravenous MgSO 4 as an adjuvant to nimodipine may reduce delayed cerebral ischemia by 34% The most recently published Intravenous Magnesium Sulphate for Aneurysmal Subarachnoid Hemorrhage [iMASH]-Trial could not demonstrate any benefit of intravenous magnesium, given within the first 48 hours after the initial bleeding event for up to 14 days, over placebo with respect to neurological outcome (Extended Glasgow Outcome Scale 5 to 8) at 6 months in 327 patients with aneurysmal subarachnoid hemorrhage.

Traumatic Brain Injury : 

Traumatic Brain Injury Traumatic brain injury is a major cause of death and disability worldwide. Its pathophysiology involves a primary event, characterized by neuronal cell death, ischemia, brain edema, and others, followed by secondary insults of multifactorial nature, which are believed to exacerbate the neurologic damage. Temkin et al. randomized 499 patients with moderate or severe traumatic head injury to either placebo or MgSO 4 within 8 h after injury continuing for 5 days and targeting serum concentrations of 1.0–1.85 mm or 1.25–2.5 mm. Magnesium did not have any benefit on the primary outcome measure based on mortality, seizures, functional measures, or neuropsychologic tests when assessed 6 months after injury. In contrast, Dhandapani et al. reported a favorable outcome in 30 patients with closed traumatic brain injury randomized to MgSO 4 within 12 h after injury

Spinal Cord Injury : 

Spinal Cord Injury Once primary injury to the spinal cord has occurred, reduction of secondary injury and ongoing ischemia by stabilizing hemodynamics and spinal perfusion pressure is most important. Magnesium has proven its neuroprotective potential in experimental spinal cord injury. Whether these effects translate to the clinical setting remains to be evaluated in large clinical trials.

Magnesium and Myocardial Infarction : 

Magnesium and Myocardial Infarction Acute myocardial infarction and related arrhythmias are still one of the major causes of death in the United States and most Western countries Mechanisms of Action Magnesium was found to induce coronary and systemic vasodilation, to improve metabolism of cardiomyocytes, and to attenuate ischemia–reperfusion injury of myocardial tissue. Many of these protective effects have been ascribed to calcium antagonism because calcium overload is the leading cause of myocardial cell death

PowerPoint Presentation: 

Na + /K + adenosine 5′-triphosphatase and Ca 2+ adenosine 5′-triphosphatase are important regulators of myocardial membrane stability. Magnesium is a cofactor of both enzymes, and additional substitution was shown to decrease membrane excitability. In addition, magnesium prolongs the absolute refractory period and shortens the relative refractory period, thereby reducing the incidence of infarction-related arrhythmias.

Clinical Data : 

Clinical Data In humans, hypomagnesemia is associated with a higher incidence of lethal arrhythmias after acute myocardial infarction, whereas intravenous administration of magnesium reduced early mortality. MgSO 4 (50 ml for the first 24 h and 12 mmol for the second 24 h) decreased 30-day mortality to 6.7% (17% for control patients) when given within 3 h after hospital admission

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Leicester Intravenous Magnesium Intervention Trial, 1992. In the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2), 2,316 patients with assumed myocardial infarction were included and received either 8 mmol MgSO 4 for 5 min, followed by 65 mmol for 24 h, or placebo. Mortality at 28 days in the treatment group was significantly ( P = 0.04) less than that of control patients.

Fourth International Study of Infarct Survival, 1995. : 

Fourth International Study of Infarct Survival, 1995. In the fourth International Study of Infarct Survival (ISIS-4), 58,050 patients with suspected myocardial infarction were included and randomized to either MgSO 4 treatment (8 mmol for 15 min, followed by 72 mmol over 24 h) or standard care. Thirty-five days after hospital admission, an insignificant increase in mortality (6%) as well as a significantly higher rate of bradycardia, heart failure, and death caused by cardiogenic shock ( P < 0.001) after magnesium treatment were observed. The heart failure and death rates were suggested to result from significant induced hypotension after magnesium administration.

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Probable explanations for the controversial results of LIMIT-2 and ISIS-4 relate to the differences in timing of magnesium administration, dosing, and a low control group mortality rate in ISIS-4. Cardioprotective effects of magnesium were shown to require high serum concentrations at the time of reperfusion. In LIMIT-2, the median time from onset of chest pain to randomization was 3 h compared with 8 h in the ISIS-4 Trial. According to the protocol, patients in LIMIT-2 began receiving magnesium when thrombolytic therapy was initiated, whereas patients in ISIS-4 received magnesium after, rather than before, or with thrombolytic therapy.

Magnesium in Coronaries Trial. : 

Magnesium in Coronaries Trial. The Magnesium in Coronaries (MAGIC) Trial, a multicenter, double-blind, placebo-controlled trial, was designed to resolve these controversies by evaluating whether administration of intravenous magnesium to high-risk patients, patients older than 65 yr, or those not eligible for reperfusion therapy in the course of myocardial infarction would result in better survival. Magnesium treatment had no beneficial effects on the primary (30-day mortality) or the secondary outcome measures (incidence of heart failure).

Minor Clinical Trials : 

Minor Clinical Trials Gyamlani et al. enrolled 100 patients with diagnosed acute myocardial infarction, who received 15 g MgSO 4 over 48 h starting within 2 h of admission. However, primary (30-day infarct size) and secondary end points (ventricular arrhythmias, death, and others) were not affected.

Summary : 

Summary According to the most recent Cochrane database review analyzing 26 trials that studied the effects of intravenous magnesium on acute myocardial infarction, magnesium seems unlikely to reduce mortality after early and late treatment, after thrombolytic therapy, or when used at high doses (more than 75 mm). It may reduce the incidence of ventricular fibrillation or tachycardia or severe arrhythmias but also may increase the incidence of profound hypotension, bradycardia, and flushing. Taken together, there is no evidence for the routine use of magnesium in patients with acute myocardial infarction

Magnesium and Cardiac Arrest : 

Magnesium and Cardiac Arrest Magnesium was reported to have a beneficial effect on the incidence of cardiac arrest after refractory ventricular fibrillation. Clinical Data In a small prospective and controlled study (n = 22), normomagnesemia was directly correlated to successful resuscitation after cardiac arrest after ventricular fibrillation or tachycardia. Evaluating the effects of 2 g MgSO 4 during resuscitation after cardiopulmonary arrest, Hassan et al. included 105 patients with refractory or recurrent ventricular fibrillation not responding to initial defibrillation.

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Magnesium did not improve return of spontaneous circulation or discharge from hospital alive. Similarly, magnesium did not improve the rate of successful resuscitation, survival for 24 h, or survival until hospital discharge in a randomized, placebo-controlled trial studying 156 patients with cardiac arrest regardless of their initial rhythm. Summary Based on current literature, there is no evidence for the routine use of magnesium in patients with cardiac arrest.

Magnesium and Cardiac Arrhythmias : 

Magnesium and Cardiac Arrhythmias Although magnesium is not considered a classic antiarrhythmic drug, it may convert some types of malignant arrhythmias. Accordingly, low magnesium serum concentrations were shown to be potentially proarrhythmogenic. Mechanisms of Action Being an endogenous calcium antagonist, magnesium slows electrical activity of the sinoatrial node, prolongs atrioventricular conductance, and finally increases the refractory period of the atrioventricular node.

Clinical Data : 

Clinical Data Supraventricular Arrhythmias. Primarily studying the effects of milrinone in 1,068 patients with moderate to severe congestive heart failure (New York Heart Association III/IV), this large clinical trial also evaluated the prognostic significance of alterations in serum magnesium. There was no evidence that low serum magnesium is an independent risk factor for sudden death or all-cause death. Moran et al. reported MgSO 4 to be superior to amiodarone in conversion of acute atrial tachyarrhythmias in critically ill patients. Coleman et al. demonstrated an enhanced ability of dofetilide to successfully convert atrial fibrillation or flutter into sinus rhythm, when MgSO 4 was used in addition.

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Atrial Fibrillation after Cardiac Surgery Arrhythmias, especially atrial fibrillation, are frequently complications after cardiac surgery, with a typical time frame of 24–96 h after surgery and a peak incidence on postoperative day 2 The underlying mechanisms are multifactorial. Hypomagnesemia, caused by cardiopulmonary bypass, high-dose diuretic therapy, surgical stress, and exogenous catecholamines, is one known risk factor for the postoperative development of atrial fibrillation. Clinical trials studying the effects of perioperative magnesium prophylaxis gave conflicting results.

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Toraman et al. reported that preoperative, intraoperative, and early postoperative administration of 6 mmol MgSO 4 significantly reduced postoperative atrial fibrillation (2% vs. 21% in the control group) Alghamdi et al. described a significant risk reduction (RR 0.64; 95% CI, 0.47–0.87; P = 0.004, numbers needed to treat = 11) of atrial fibrillation after magnesium administration. Considering all of the data, current evidence for beneficial effects of magnesium in the prophylaxis of life-threatening arrhythmias after surgery is controversial. Studies conducted were small, and significant heterogeneity between different trials was present. A definite answer of whether magnesium replacement in a state of hypomagnesemia in that patient population is or is not of potential depends on the results of more large, well-designed clinical trials.

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Ventricular Arrhythmias. Current treatment options consist of cardioversion, amiodarone, and normalization of serum electrolytes, including magnesium. Two small studies demonstrated reduced and even suppressed episodes of nonsustained monomorphic ventricular tachycardia after magnesium administration. However, to date there is no solid clinical evidence recommending magnesium in the treatment or prophylaxis of monomorphic ventricular tachycardia.

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Torsades de Pointes. Torsades de pointes tachycardias certainly benefit from administration of magnesium. Malfunction of potassium channels results in delayed ventricular repolarization and inactivation of calcium channels. The late calcium influx combined with the prolonged repolarization causes early after-depolarizations, leading to torsades de pointes and associated long QT intervals. Magnesium attenuates these pathologic changes by inhibiting calcium currents, as shown by a variety of experimental and clinical data. As an urgent measure, 2 g MgSO 4 (25–50 mg/kg in children should be the drug of choice, followed by electrolyte stabilization and efforts to accelerate the basic heart rate.

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Digoxin-induced Arrhythmias. Magnesium is well established in the management of digoxin-induced tachyarrhythmias. Digoxin antibodies are the basic treatment, but in hypomagnesemic patients, especially those susceptible to digoxin-induced arrhythmias, intravenous administration of magnesium should be part of the immediate standard therapy until Fab antibodies are available (Class IIa, Level of Evidence B, AHA)

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Summary Magnesium has an essential role in normal cardiac electrophysiology, and altered serum concentrations may contribute to a variety of cardiac arrhythmias. Reflecting the current controversy of existing evidence, the majority of guidelines (American College of Cardiology, AHA, American College of Chest Physicians, European Society of Cardiology) for managing atrial fibrillation or postoperative cardiac arrhythmias does not recommend magnesium for standard therapy, whereas the European Association for Cardio-Thoracic Surgery approves prophylaxis with magnesium for minimizing the incidence of atrial fibrillation in patients undergoing cardiac surgery. However, there is a clear recommendation for MgSO 4 in patients with long QT syndrome and episodes of torsades de pointes (Class IIa, Level of Evidence B, AHA)

Magnesium and Side Effects : 

Magnesium and Side Effects Intravenous administration of magnesium generally is associated with minor side effects. It may provoke burning sensation or pain on injection and induce agitation, drowsiness, and nausea. Patients also may experience headache, dizziness, and muscle weakness or report hypotension and bradycardia.

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In eclampsia, approximately 25% of women treated with magnesium experience side effects, mainly flushing. Magnesium may increase the risk of postpartum hemorrhage and respiratory depression. Because magnesium crosses the placenta, it may induce neonatal lethargy, hypotension, and rarely respiratory depression after prolonged administration (more than 48 h).

Table 4: 

Table 4 Copyright © 2011 Anesthesiology. Published by Lippincott Williams & Wilkins. 78

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Mg blockade at the neuromuscular junction is the result of A reduction of the amount of acetylcholine released from motor nerve terminals; A decrease in the depolarizing action of acetylcholine at the endplate; Depression of muscle fibre membrane excitability.

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Clinical situations in which glycemia remains elevated despite increased insulin doses are frequent in intensive care. In fact, insulin resistance increases as the serum Mg concentration decreases, with Mg acting as a second messenger for insulin. Diuretics increase renal excretion of Mg and can cause hypomagnesemia. Gentamicin treatment can also induce hypomagnesemia through renal loss of Mg, which ceases once treatment is stopped

Prospects: 

Prospects Recent studies could lead to the establishment of new indications for Mg. In patients with tetanus, Mg infused at doses providing serum concentrations of 2 to 4 mmol·L–1 allowed good control of spasms and muscle rigidity. Intubation and ventilation were only required for 43% of patients, and the overall death rate was 12%

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Fluoroquinolones, which are toxic for tendons and cartilage, are Mg ion chelators largely involved in cartilage biochemistry. A recent animal study found that fluoroquinolones induced a high rate of cartilaginous lesions in immature rats with Mg deficiency, whereas rats without deficiency had no lesions. A correction of hypomagnesemia might be necessary in this context.

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Mg or calcium deficiency seems likely in those patients treated by oxaliplatin who show neurotoxic clinical side effects characteristic of tetany or myotonia. The toxicity of oxaliplatin for the neuron is related to a decrease in the inward sodium current amplitude resulting in a reduction of the action potential amplitude, e.g., in the case of calcium chelating substances. The role of Mg or calcium in preventing oxaliplatin neurotoxicity has been suggested,and a prospective study has been initiated to confirm the neuroprotective effects of calcium and Mg.

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Conclusion Magnesium plays a key role in numerous physiologic processes, and various indications have been proposed for its use as a therapeutic agent. Despite promising experimental data, large clinical trials often have provided conflicting results, questioning the expected efficacy of magnesium in several clinical settings. Additional research is required to complete our understanding of when and how to use magnesium therapeutically.

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Nevertheless, there are conditions that benefit from magnesium therapy, such as preeclampsia, eclampsia, and torsades de pointes arrhythmias. Maintenance of magnesium serum concentrations within normal physiologic limits is desirable, and with respect to its well-established safety profile, one may consider magnesium an additional alternative for the specific described pathologies when standard therapy fails.

Magnesium anaesthesia is not a New it dates back to : 

Magnesium anaesthesia is not a New it dates back to JAMA. 1950;143(5):508 Investigations on the Course and Localisation of Magnesium Anesthesia: A Comparison with Ether Anesthesia at forsvares for den medicinske Doktorgrad, København, 1947. Paper. Pp. 189, with 18 illustrations. Nyt Nordisk Forlag, Arnold Busck, Copenhagen, 1948. This small volume, translated from the Danish presents a concise review of the pharmacologic effects of magnesium salts, particularly as compared with the effects of ether. It contains reports of considerable experimental work performed by the author as well as an excellent review of the literature on the subject. Its content is largely technical and experimental and will be most interesting to the pharmacologist and experimental worker rather than to the clinical anesthesiologist.

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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.

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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.

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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.

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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.

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I.V. infusion of magnesium sulphate during spinal anaesthesia improves postoperative analgesia J.-Y. Hwang 1 , H.-S. Na 1 , Y.-T. Jeon 1 , Y.-J. Ro 2 , C.-S. Kim 2 and S.-H. Do 1 , * Abstract in Br. J. Anaesth. January (2010) 104 (1): 89-93. Background In a randomized, double-blind, prospective study, we have evaluated the effect of i.v. infusion of magnesium sulphate during spinal anaesthesia on postoperative analgesia and postoperative analgesic requirements. Methods Forty patients undergoing total hip replacement arthroplasty under spinal anaesthesia were included. After the induction of spinal anaesthesia, the magnesium group (Group M) received magnesium sulphate 50 mg kg −1 for 15 min and then 15 mg kg −1 h −1 by continuous i.v. infusion until the end of surgery. The saline group (Group S) received the same volume of isotonic saline over the same period. Serum magnesium concentrations were checked before the induction of anaesthesia, immediately after surgery, and at 1 and 24 h after surgery. Results Postoperative pain scores were significantly lower in Group M at 4, 24, and 48 h after surgery ( P <0.05). Cumulative postoperative PCA consumptions were also significantly lower in Group M at 4, 24, and 48 h after surgery ( P <0.05). Postoperative magnesium concentrations were higher in Group M ( P <0.05 at 4, 24, and 48 h after surgery), but no side-effects associated with hypermagnesemia were observed. Haemodynamic variables and the incidences of shivering, nausea, and vomiting were similar in the two groups. Conclusions I.V. magnesium sulphate administration during spinal anaesthesia improves postoperative analgesia.

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Magnesium sulphate for treatment of tetanus in adults PJ Mathew , T Samra , J Wig Department of Anaesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India Summary in Anaesthesia and Intensive Care Volume 38, Issue 1 January 2010 There are reports that suggest that magnesium sulphate alone may control muscle spasms thereby avoiding sedation and mechanical ventilation in tetanus, but this has not been confirmed. We examined the efficacy and safety of intravenous magnesium sulphate for control of rigidity and spasms in adults with tetanus. A prospective clinical study of intravenous magnesium sulphate was carried out over a period of two years in a tertiary care teaching hospital. In addition to human tetanus immunoglobulin and parenteral antibiotics, patients with tetanus received magnesium sulphate 70 mg/kg intravenously followed by infusion. The infusion was increased by 0.5 g/hour every six hours until cessation of spasms or abolishment of patellar tendon jerk. The primary outcome measure was efficacy determined by control of spasms. Secondary outcomes included frequency of autonomic instability, duration of ventilatory support, hospital stay and mortality. Thirty-three patients were enrolled. At presentation, the incidence of severity of tetanus was as follows: Grade I: 5 (15%), Grade II: 13 (39%), Grade III: 14 (42%) and Grade IV: 1 (3%). Rigidity and mild spasms were controlled with magnesium therapy alone in six patients; all were Grades I or II. Additional sedatives were required in severe forms of tetanus. The average duration of ventilatory support was 18.3±16.0 days and the overall mortality was 22.9%. Asymptomatic hypocalcaemia was a universal finding. Magnesium sulphate therapy alone may not be efficacious for the treatment of severe tetanus.

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Magnesium sulphate for treatment of severe tetanus: a randomised controlled trial Dr CL Thwaites , LM Yen HT Loan , TTD Thuy , GE Thwaites , K Stepniewska , N Soni , Prof NJ White , Prof JJ Farrar Summary in The Lancet, Volume 368, Issue 9545 , Pages 1436 - 1443, 21 October 2006 Background: The most common cause of death in individuals with severe tetanus in the absence of mechanical ventilation is spasm-related respiratory failure, whereas in ventilated patients it is tetanus-associated autonomic dysfunction. Our aim was to determine whether continuous magnesium sulphate infusion reduces the need for mechanical ventilation and improves control of muscle spasms and autonomic instability. Methods: We did a randomised, double blind, placebo controlled trial in 256 Vietnamese patients over age 15 years with severe tetanus admitted to the Hospital. Participants were randomly assigned magnesium sulphate (n=97) or placebo solution (n=98) intravenously for 7 days. The primary outcomes were requirement of assisted ventilation and of drugs to control muscle spasms and cardiovascular instability within the 7-day study period. Findings: No patients were lost to follow-up. There was no difference in requirement for mechanical ventilation between individuals treated with magnesium and those receiving placebo (odds ratio 0·71, 95% CI 0·36—1·40; p=0·324); survival was also much the same in the two groups. However, compared with the placebo group, patients receiving magnesium required significantly less midazolam (7·1 mg/kg per day [0·1—47·9] vs 1·4 mg/kg per day [0·0—17·3]; p=0·026) and pipecuronium (2·3 mg/kg per day [0·0—33·0] vs 0·0 mg/kg per day [0·0—14·8]; p=0·005) to control muscle spasms and associated tachycardia. Individuals receiving magnesium were 4·7 (1·4—15·9) times less likely to require verapamil to treat cardiovascular instability than those in the placebo group. The incidence of adverse events was not different between the groups. Interpretation Magnesium infusion does not reduce the need for mechanical ventilation in adults with severe tetanus but does reduce the requirement for other drugs to control muscle spasms and cardiovascular instability.

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Int J Obstet Anesth. 2010 Oct;19(4):401-4. The effect of adding magnesium sulphate to epidural bupivacaine and fentanyl in elective caesarean section using combined spinal-epidural anaesthesia: a prospective double blind randomised study. Yousef AA , Amr YM . BACKGROUND: Combined spinal-epidural anaesthesia is commonly used for elective caesarean section. Intrathecal injection produces rapid onset with minimal doses of local anaesthetic and epidural administration can be used to prolong the block. Our study examined the effects of adding magnesium sulphate to epidural bupivacaine and fentanyl in patients undergoing elective caesarean section using combined spinal-epidural anaesthesia. METHODS: Women ASA physical status I or II at term were recruited. All received 2 mL intrathecal 0.5% hyperbaric bupivacaine, 10 mL epidural 0.25% plain bupivacaine with fentanyl 100 μg, and were randomly allocated to receive either 10 mL of epidural 0.9% sodium chloride or 10 mL epidural 5% magnesium sulphate. The quality of surgical anaesthesia, incidence of hypotension, Apgar scores, intraoperative pain assessment, onset of postoperative pain, sedation scores and side effects were recorded in the postoperative period. RESULTS: Ninety women were recruited. There was no difference in the time taken for the block to reach T4 sensory level, time to reach the highest level of sensory block, time interval between first neuraxial injection and onset of surgery between the groups. Women who received magnesium had greater motor block and muscle relaxation (P<0.05). Apgar scores were 7 or more in almost all neonates in both groups. There was no significant difference in the incidence of hypotension, nausea and vomiting and duration of motor blockade between the groups. Women who received magnesium showed less shivering and later onset of post operative pain (P<0.05). CONCLUSION: The addition of magnesium to epidural bupivacaine and fentanyl in women undergoing elective caesarean section with combined spinal-epidural anaesthesia improved intraoperative conditions and the quality of postoperative analgesia.

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Knee Surgery, Sports Traumatology, Arthroscopy Volume 19, Number 6 , 1043-1046, JUNE 2011 In vitro assessment of human chondrocyte viability after treatment with local anaesthetic, magnesium sulphate or normal saline Local anaesthetic agents are often used as an intra-articular analgesic following arthroscopic procedures. However, there is increasing evidence of a potential toxic effect to chondrocytes within the articular cartilage. The aim of this study was to compare the effect on human chondrocyte viability of treatment with bupivacaine, levobupivacaine and ropivacaine. The second aim was to compare the effect on chondrocyte viability of the local anaesthetics with magnesium, a potential alternative analgesic agent. Conclusion: A dose-dependent reduction in chondrocyte viability after treatment with common local anaesthetic agents was confirmed. Local anaesthetic agents had a greater deleterious effect on chondrocytes than did 10% magnesium sulphate. These findings suggest the need for continuing caution with the use of intra-articular local anaesthetic. Magnesium sulphate is a potential alternative intra-articular analgesic agent.

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Effect of intra-operative magnesium sulphate on pain relief and patient comfort after major lumbar orthopaedic surgery Ch. Levaux, V. Bonhomme, P. Y. Dewandre, J. F. Brichant, P. Hans Anaesthesia Volume 58, Issue 2, pages 131–135, February 2003 During surgery, neuromuscular block recovery was longer in the magnesium group. Postoperative opioid consumption and pain scores were lower in the magnesium group. The first night's sleep and the global satisfaction scores were better in the magnesium group. The results of the study support magnesium sulphate as a useful adjuvant for postoperative analgesia after major lumbar surgery.

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Thanx