Substances Included Synonyms

Therapeutic Toxic Class

A)

Specific Substances

A)

1) MAGNESIUM
2) MAGNESIO (Italian)
3) MAGNESIUM CLIPPINGS
4) MAGNESIUM PELLETS
5) MAGNESIUM POWDERED
6) MAGNESIUM RIBBONS
7) MAGNESIUM TURNINGS
8) RMC
9) CAS 7439-95-4

1) MAGNESIUM ALLOYS
2) MAGNESIUM SCRAP
3) MAGNESIUM OXIDE FUME
4) MAGNESIUM METAE
5) MAGNESIUM, IN PELLETS, TURNINGS OR RIBBON
6) MAGLITE S
7) MAGLITE DE
8) MAGNESIA MONOXIDE
9) MAGNESIA FUME
10) MAGNESIA ALBA
11) MAGNESA
12) MAGLITE Y
13) MAGNESIUM CARBONATE, BASIC
14) MAGLITE K
15) MAGLITE D
16) LIGHT MAGNESIA
17) HEAVY MAGNESIUM OXIDE
18) HEAVY MAGNESIA
19) HEAVY CALCINED MAGNESIA
20) ANSCOR P
21) SEASORB

1) MAGNESIUM SULFATE
2) Epsom salt
3) MAGNESIUM HYDROXIDE
4) MAGNESIUM CITRATE

1.2.1) MOLECULAR FORMULA
1) Mg

Available Forms Sources

A)

1) Several "non absorbed" antacids contain magnesium including Maalox(R), Camalox(R), Ducon(R), Milk of Magnesia, Mylanta(R), Digel(R), Gelusil(R). See content below.

Table 1. Magnesium Content of Pharmaceuticals (1 mEq = 12 mg)
Product	Magnesium (mg)	Magnesium (mEq)
Gelusil susp	82/5 mL	6.8/5 mL
Gelusil M susp	82/5 mL	6.8/5 mL
Maalox susp	82/5 mL	6.8/5 mL
Maalox Plus	82/5 mL	6.8/5 mL
Maalox TC	124/5 mL	10.3/5 mL
Magnesium gluconate tablet	27/500 mg	2.25/tab
Chelated Magnesium tablet	100 mg/500 mg	8.3/tab
Mg plus Protein	133 mg/tablet	11.1/tab
Magnesium sulfate	2880/30 g	240/30 g
Magnesium sulfate inj 10%	97.56/10 mL	8.1/10 mL
Magnesium sulfate inj 50%	97.56/2 mL	8.1/2 mL
Mylanta	82/5 mL	6.8/5 mL
Mylanta II	164/5 mL	13.7/5 mL
Suby G	228/100 mL	19/100 mL
Magnesium citrate	2,880/300 mL	240/300 mL
Magnesium hydroxide	408/g	34/g
Milk of Magnesia	995/30 mL	83/30 mL

2) Renacidin contains magnesium hydroxycarbonate 75-87 grams and magnesium acid citrate 9 to 15 grams per 300 gram bottle. Urogate (Suby G) solution contains 0.38% magnesium oxide.
3) DOLOMITE, a natural source of magnesium and calcium, was reported by Roberts (1981) to contain the following minerals and toxic metals

SUBSTANCE	CONCENTRATION (ppm)
Aluminum	187.1
Arsenic	24.0
Cadmium	2.3
Chromium	76.7
Iron	305.7
Lead	34.9
Manganese	91.3
Mercury	11.6
Nickel	12.9
Phosphorus	92.0
Silicon	41.8
Zinc	10.6

4) Hypermagnesemia with hypercalcemia occurred following ingestion of Dead Sea water while bathing. Dead Sea water contains high concentrations of bromide, calcium, magnesium, and sodium (Oren et al, 1987).

B)

1) Magnesium sulfate (Epsom salt) is one of the most commonly employed household purgatives. Hypermagnesemia has occurred following irrigation of the renal pelvis with magnesium-containing urologic solutions for dissolution of struvite urinary stones (Jenny et al, 1978; Cato & Tulloch, 1974; Wilson et al, 1986).

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) USES: Magnesium is available in many forms and has many different medical uses, including as an antacid and laxative, anticonvulsant, treatment of torsades de pointes, pre-eclampsia, management of acute asthma exacerbation, hydrofluoric acid ingestion, enema, and electrolyte supplement. Magnesium is an essential electrolyte in the body and is a cofactor in many enzyme systems. Industrially, magnesium is used as a component of aluminum alloys, in die-casting alloyed with zinc, to remove sulfur in the production of iron and steel, and for the production of titanium.
B) PHARMACOLOGY: When taken orally, magnesium promotes bowel evacuation by osmotic retention of fluid which distends the colon and increases peristaltic activity. Parenteral magnesium decreases acetylcholine in motor nerve terminals and acts on myocardium by slowing rate of S-A node impulse formation and prolonging conduction time as well as stabilizing excitable membranes. Magnesium is also necessary for the movement of other electrolytes (calcium, sodium and potassium) in and out of cell.
C) TOXICOLOGY: In overdose, magnesium impairs neuromuscular transmission, manifested as weakness and hyporeflexia.
D) EPIDEMIOLOGY: Thousands of exposures occur every year, but severe manifestations are very rare. Severe toxicity is most common after intravenous infusion over multiple hours (usually for pre-eclampsia), and can occur after chronic excessive doses, especially in the setting of renal insufficiency. Severe toxicity has been reported after acute ingestion but is very rare.
E) WITH THERAPEUTIC USE

1) Adverse effects seen with magnesium sulfate include adverse effects on neuromuscular function and flushing (IV, dose-related), hypotension (IV, rate-related), and vasodilation (IV, rare-related). Magnesium sulfate may also cause diarrhea. Magnesium hydroxide has many drug interactions secondary to its antacid effect.

F) WITH POISONING/EXPOSURE

1) MILD TO MODERATE TOXICITY: Nausea and vomiting are common with oral exposure. Flushing can occur most often with intravenous administration. Magnesium dust can irritate the eye and mucous membranes of the upper respiratory tract causing an atrophic nasopharyngitis. Metal fume fever can result from inhalation of magnesium fumes.
2) SEVERE TOXICITY: Severe toxicity occurs most often after intravenous infusions. It can also occur after chronic excessive oral doses, often in patients with renal insufficiency. Early manifestations are lethargy, hyporeflexia, followed by weakness, paralysis, hypotension, ECG changes (prolonged PR and QRS intervals), CNS depression, seizures, and respiratory depression.

0.2.20)

A) Magnesium sulfate is classified as FDA pregnancy category A . Magnesium sulfate and the citric acid, magnesium oxide, and sodium picosulfate combination are classified as FDA pregnancy category B.

0.2.21)

A) At the time of this review, no studies were found on the potential carcinogenic activity of magnesium in humans or experimental animals.

Laboratory Monitoring

A)

B)

C)

D)

E)

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) For mild to moderate exposures, supportive care and removal of further magnesium exposure are the mainstays of treatment. Administer antiemetics for nausea and vomiting. Manage mild hypotension with IV fluids. Administer intravenous fluids to promote magnesium diuresis.

B) MANAGEMENT OF SEVERE TOXICITY

1) For patients with severe toxicity, treatment is symptomatic and supportive. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids. IV calcium chloride can be used to temporarily ameliorate respiratory depression until more definitive therapy can be instituted. Airway management may be necessary for patients with CNS depression or severe weakness. Emergent hemodialysis should be performed in patients with severe toxicity (dysrhythmias, persistent hypotension, severe CNS depression, and respiratory depression).
2) INHALATION EXPOSURE: Move patients into fresh air and away from magnesium dust. DERMAL EXPOSURE: Wash exposed area with soap and water.
3) EYE EXPOSURE: Irrigate eyes with water or normal saline and remove any particulate matter.
4) INTRATHECAL EXPOSURE: Up to 100 mg of intrathecal magnesium sulfate has been used in anesthesia and is well-tolerated. After very large intrathecal overdose, immediate drainage of CSF (20 to 40 mL) should be considered.
5) RECTAL EXPOSURE: Treatment is primarily supportive.

C) DECONTAMINATION

1) PREHOSPITAL: Gastrointestinal decontamination is not indicated as activated charcoal does not bind to magnesium. Wash exposed skin with soap and water; irrigate exposed eyes.
2) HOSPITAL: Gastrointestinal decontamination is not indicated as activated charcoal does not bind magnesium. Wash exposed skin with soap and water; irrigate exposed eyes.

D) AIRWAY MANAGEMENT

1) Endotracheal intubation may be necessary if patients develop CNS, neuromuscular, or respiratory depression.

E) ANTIDOTE

1) None

F) ENHANCED ELIMINATION PROCEDURE

1) Hemodialysis is the most effective method to remove significant quantities of magnesium and may reverse life-threatening symptoms within 30 minutes. Emergent dialysis should be considered in any patients with severe toxicity (hypotension, dysrhythmias, severe CNS depression, respiratory depression) or patients with moderate effects and severe renal insufficiency.

G) PATIENT DISPOSITION

1) HOME CRITERIA: Patients who are asymptomatic and exposures within therapeutic range may stay at home. Patients with minimal symptoms that are improving may also be monitored at home.
2) OBSERVATION CRITERIA: Patients with systemic or moderate to severe symptoms should be sent to a healthcare facility for observation until symptoms are clearly improving and the patient is clinically stable.
3) ADMISSION CRITERIA: Patients with persistent weakness or magnesium concentrations that are not declining despite hydration should be admitted. Patients with hypotension, ECG changes, CNS or respiratory depression should be admitted to an ICU setting. Patients should remain admitted until symptoms are clearly improving and clinically stable.
4) CONSULT CRITERIA: Consult a medical toxicologist or poison center for any patient with severe toxicity or in whom the diagnosis is unclear. Consult a nephrologist for hemodialysis in patients with severe toxicity. Patients with severe toxicity or renal insufficiency may require transfer to a hospital that can perform emergent hemodialysis.

H) PITFALLS

1) The biggest pitfalls in managing these patients are not considering hypermagnesemia as a diagnosis or not monitoring patients closely enough for signs of toxicity.

I) PHARMACOKINETICS

1) About 40% to 60% is absorbed after ingestion; absorption decreases as higher doses. Protein binding: about 30%. Vd: 0.2 to 0.4 L/kg. Renal elimination. Distribution primarily to bone (50%).

J) TOXICOKINETICS

1) In higher doses, smaller percentage of oral magnesium is absorbed via the GI tract. During hypermagnesemia, up to 97% of magnesium may be excreted renally. Maximum magnesium clearance is directly proportional to creatinine clearance. Elimination half-life has been reported to be 27.7 hours following an overdose of 400 mEq magnesium in an adult.

K) PREDISPOSING CONDITIONS

1) Patients with renal failure and metabolic derangements (such as anorexia) may develop magnesium toxicity or lower doses. Patients with underlying neuromuscular diseases such as myasthenia gravis may experience adverse effects on neuromuscular function at lower magnesium concentrations.

L) DIFFERENTIAL DIAGNOSIS

1) The differential diagnosis for magnesium overdose includes other medications or substances that can cause gastrointestinal distress, CNS depression, cardiac abnormalities, hypotension, bradycardia, and muscle paralysis.

0.4.3)

A) INHALATION EXPOSURE: Move patients into fresh air and away from magnesium dust. DERMAL EXPOSURE: Wash exposed area with soap and water.

0.4.4)

A) EYE EXPOSURE: Irrigate eyes with water or normal saline and remove any particulate matter.

Range Of Toxicity

A)

B)

C)

D)

E)

F)

G)

Clinical Effects

Summary Of Exposure

A)

B)

C)

D)

E)

1) Adverse effects seen with magnesium sulfate include adverse effects on neuromuscular function and flushing (IV, dose-related), hypotension (IV, rate-related), and vasodilation (IV, rare-related). Magnesium sulfate may also cause diarrhea. Magnesium hydroxide has many drug interactions secondary to its antacid effect.

F)

1) MILD TO MODERATE TOXICITY: Nausea and vomiting are common with oral exposure. Flushing can occur most often with intravenous administration. Magnesium dust can irritate the eye and mucous membranes of the upper respiratory tract causing an atrophic nasopharyngitis. Metal fume fever can result from inhalation of magnesium fumes.
2) SEVERE TOXICITY: Severe toxicity occurs most often after intravenous infusions. It can also occur after chronic excessive oral doses, often in patients with renal insufficiency. Early manifestations are lethargy, hyporeflexia, followed by weakness, paralysis, hypotension, ECG changes (prolonged PR and QRS intervals), CNS depression, seizures, and respiratory depression.

Vital Signs

3.3.3)

A) WITH POISONING/EXPOSURE

1) A subjective feeling of heat and extreme thirst may be noted.
2) Hypothermia may occur following magnesium toxicity (Sullivan & Berman, 2000). Hypothermia was reported in a 42-year-old female with hypermagnesemia due to laxative use (McLaughlin & McKinney, 1998) and hypothermia of 90.9 degrees F was reported in an massive overdose of magnesium-containing laxatives (Qureshi & Melonakos, 1996).
3) CASE REPORT: A 16-year-old girl who received a bone marrow transplant 45 days before presentation, developed hypermagnesemia (magnesium level 5.9 mmol/L) resulting in hypotension, hypothermia, and coma after ingesting 15 mL of magnesium-containing antacid every 2 hours instead of 4 times daily. Following supportive care, she recovered completely (Jaing et al, 2002).

Heent

3.4.3)

A) WITH POISONING/EXPOSURE

1) BLURRED VISION

a) Three out of 6 patients were magnesium poisoned when a dialysate solution was prepared with 15 mEq instead of 1.5 mEq of magnesium chloride per liter. They complained of blurred vision. No objective visual defect could be identified (Grant & Schuman, 1993).

2) IRRITATION

a) Magnesium oxide dust may cause slight ocular irritation following industrial exposures (Grant & Schuman, 1993).

Cardiovascular

3.5.2)

A) CARDIAC ARREST

1) WITH POISONING/EXPOSURE

a) Cardiac arrest has been reported in patients with severe hypermagnesemia (Birrer et al, 2002; Zwanger, 1986; Qureshi & Melonakos, 1996).
b) CASE REPORT: Cardiac arrest was reported in 2 patients given 20 grams magnesium sulfate as an IV bolus erroneously instead of 2 grams IV for alcohol withdrawal. One patient was successfully resuscitated and the other patient died 3 days later (Vissers & Purssell, 1995).
c) CASE REPORT/PEDIATRIC: Cardiac arrest in a 2.5-year-old boy due to severe hypermagnesemia (3.2 mmol/L; normal <1.2 mmol/L) from magnesium oxide supplements given for constipation was reported. The child was resuscitated, but died within 24 hours following persistent bradycardia and heart block (Kulkarni et al, 1999).

B) HYPOTENSIVE EPISODE

1) WITH THERAPEUTIC USE

a) Therapeutic doses of magnesium sulfate for preeclampsia produced hypotension (diastolic 40 to 50 mmHg) (Bourgeois et al, 1986) .

2) WITH POISONING/EXPOSURE

a) At serum magnesium concentrations of 6.0 to 7.0 mEq/L, somnolence and hypotension occur (Razavi & Somers, 2000). Overdoses may result in refractory hypotension, shock and cardiac arrest (Birrer et al, 2002; Qureshi & Melonakos, 1996).
b) Laxative use has resulted in hypermagnesemia with hypotension (McLaughlin & McKinney, 1998).
c) CASE REPORT/PEDIATRIC: A 14-year-old girl with severe constipation and ileus and without pre-existing renal dysfunction presented with lethargy and hypotension (BP 70/40 mm Hg) after receiving 18 g/day of magnesium hydroxide-containing cathartic for 7 days. Serum magnesium concentration was elevated at 14.9 mg/dL with a low ionized calcium 1.06 mg/dL. She experienced bradycardia (30 BPM) and respiratory arrest one hour later. Following supportive therapy and hemodialysis, she made a full recovery and was discharged without recurrence of hypermagnesemia (Kutsal et al, 2007).
d) CASE REPORT/INFANT: Two premature infants (born at 29 weeks and 28 weeks, respectively) developed a sudden onset of hypotension, bradycardia, apnea and hypotonia following inadvertent excessive exposure to magnesium found in the parenteral nutrition. Magnesium levels were 43.1 mEq/L and 45 mEq/L (normal 1.6 to 2.1 mEq/L), respectively. Both infants were treated successfully with only mild gross motor developmental delay noted in one infant at 4 and 8 months (Ali et al, 2003).
e) CASE REPORT: A 16-year-old girl who received a bone marrow transplant 45 days before presentation, developed hypermagnesemia (magnesium level 5.9 mmol/L) resulting in hypotension, hypothermia, and coma after ingesting 15 mL of magnesium-containing antacid every 2 hours instead of 4 times daily. Following supportive care, she recovered completely (Jaing et al, 2002).

C) BRADYCARDIA

1) WITH POISONING/EXPOSURE

a) Bradycardia and conduction delays with heart block may occur with severe hypermagnesemia (Kulkarni et al, 1999).
b) CASE REPORTS

1) PEDIATRIC: A 14-year-old girl with severe constipation and ileus and without pre-existing renal dysfunction presented with lethargy and hypotension after receiving 18 g/day of magnesium hydroxide-containing cathartic for 7 days. Serum magnesium concentration was elevated at 14.9 mg/dL with a low ionized calcium (1.06 mg/dL). ECG showed prolonged corrected QT interval (0.58 seconds) and first-degree atrioventricular block (PR interval, 0.22 seconds). She experienced bradycardia (30 BPM) and respiratory arrest one hour later. Following supportive therapy and hemodialysis, she made a full recovery and was discharged without recurrence of hypermagnesemia (Kutsal et al, 2007).
2) PEDIATRIC: Two premature infants (born at 29 weeks and 28 weeks, respectively) developed a sudden onset of hypotension, bradycardia, apnea and hypotonia following inadvertent excessive exposure to magnesium found in the parenteral nutrition. Magnesium levels were 43.1 mEq/L and 45 mEq/L, respectively. Both infants were treated successfully with only mild gross motor developmental delay noted in one infant at 4 and 8 months (Ali et al, 2003).
3) ADULT: Zwanger (1986) reported a patient with hypermagnesemia from ingestion of epsom salts for constipation (Zwanger, 1986).

a) The ECG demonstrated a sinus rate of 60, inverted T waves in leads II, III, AVF, and V2 through V6, a PR interval of 0.20 seconds, QRS interval of 0.10 seconds and a prolonged QT interval. This patient also had a history of coronary artery disease and hypertension. Magnesium in the blood was 12.5 mg/dL.

4) PREGNANT FEMALE: A pregnant woman at 32 weeks gestation inadvertently received 30 grams of intravenous magnesium sulfate over a few minutes. She quickly became unresponsive to pain and then became cyanotic and apneic, with bradycardia and no measurable peripheral pulse. She was treated with oxygen, calcium gluconate, forced diuresis and recovered (Bruhwiler et al, 1994).

D) ELECTROCARDIOGRAM ABNORMAL

1) WITH POISONING/EXPOSURE

a) Prolonged PR, QRS and QT intervals may occur following magnesium overdoses (Qureshi & Melonakos, 1996). At magnesium serum concentrations as low as 5 mEq/L, PR, QRS, and QT prolongation may occur (Razavi & Somers, 2000).
b) CASE REPORT: A pregnant woman with severe pre-eclampsia who required an emergency caesarean section, developed ECG abnormalities after receiving a loading dose of magnesium sulfate (4 g of 50% solution [8 mL]) and an entire syringe (25 g) of magnesium sulfate over approximately 40 minutes (Buettner, 2011).
c) CASE REPORT: A 31-year-old woman with normal renal function developed severe hypermagnesemia (magnesium level 9.8 mmol/L (23.6 mg/dL)) following chronic gargling with Epsom salt for halitosis. She experienced coma, hypotension, acute renal failure, and multiple episodes of asystole and ventricular fibrillation requiring repeated defibrillation. Despite intensive care, including hemodialysis, she died of a cardiac arrest (Birrer et al, 2002).
d) A premature infant (born at 28 weeks) developed QT interval prolongation after inadvertent excessive exposure to magnesium via total parenteral nutrition. Serum magnesium level peaked at 45 mEq/L (Ali et al, 2003).
e) CASE REPORT: A 50-year-old female, presenting with hypermagnesemia from massive laxative dose, experienced first-degree AV block with non-specific ST-segment changes, QRS complex of 0.08 sec, prolonged QT interval of 0.36 sec, and PR interval of 0.28 sec. Her condition improved over 7 days with IV calcium, saline infusions, cardiorespiratory support and supportive therapy (Qureshi & Melonakos, 1996).
f) CASE REPORT/PEDIATRIC: A 14-year-old girl with severe constipation and ileus and without pre-existing renal dysfunction presented with lethargy and hypotension (BP 70/40 mm Hg) after receiving 18 g/day of magnesium hydroxide-containing cathartic for 7 days. Serum magnesium concentration was elevated at 14.9 mg/dL with a low ionized calcium (1.06 mg/dL). ECG showed prolonged corrected QT interval (0.58 seconds) and first-degree atrioventricular block (PR interval, 0.22 seconds). She experienced bradycardia (30 BPM) and respiratory arrest one hour later. Following supportive therapy and hemodialysis, she made a full recovery and was discharged without recurrence of hypermagnesemia (Kutsal et al, 2007).

Respiratory

3.6.2)

A) ACUTE RESPIRATORY INSUFFICIENCY

1) WITH THERAPEUTIC USE

a) Respiratory depression may occur. Severe respiratory depression associated with elevation in serum magnesium has been reported in a patient following irrigation of the renal pelvis via nephrostomy tube with a urologic solution containing magnesium oxide (Jenny et al, 1978).

B) HYPOREFLEXIA

1) WITH THERAPEUTIC USE

a) LOSS OF REFLEXES: Loss of deep tendon reflexes (Mg level 5 mEq/L) usually precedes respiratory depression (Mg level 10 mEq/L) and provides a useful clinical monitor in the therapeutic setting (Zwanger, 1986).

2) WITH POISONING/EXPOSURE

a) LOSS OF REFLEXES: Loss of deep tendon reflexes (Mg level 5 mEq/L) usually precedes respiratory depression (Mg level 10 mEq/L) and provides a useful clinical monitor in the overdose setting (Zwanger, 1986).

C) APNEA

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Inadvertent administration of 30 grams of magnesium sulfate intravenously in an adult resulted in apnea and cyanosis (Bruhwiler et al, 1994).
b) CASE REPORT: Following an infusion of 24.7 grams of magnesium sulfate, a 29-year-old woman became rapidly comatose and apneic (Fletcher & Parr, 2000).

D) METAL FEVER

1) WITH POISONING/EXPOSURE

a) Metal fume fever can result from inhalation of magnesium fumes.

E) RESPIRATORY ARREST

1) WITH POISONING/EXPOSURE

a) Infants with elevated serum magnesium levels have demonstrated respiratory arrest (Outerbridge et al, 1973).
b) CASE REPORT/PEDIATRIC: A 14-year-old girl with severe hypermagnesemia (serum magnesium 14.9 mg/dL) experienced respiratory arrest after receiving 18 g/day of magnesium hydroxide-containing cathartic for 7 days. Following supportive therapy and hemodialysis, she made a full recovery and was discharged without recurrence of hypermagnesemia (Kutsal et al, 2007).

Neurologic

3.7.2)

A) CENTRAL NERVOUS SYSTEM DEFICIT

1) WITH POISONING/EXPOSURE

a) CNS depression may accompany elevated serum magnesium levels and cause unconsciousness or coma. Lethargy, as well as hyporeflexia, weakness and cutaneous flushing may be noted (Kutsal et al, 2007; Wilson et al, 1986; Zwanger, 1986; Qureshi & Melonakos, 1996; Nordt et al, 1996). Drowsiness and hyporeflexia generally occur at a serum magnesium level >4.0 mEq/L (Razavi & Somers, 2000).
b) PEDIATRIC: Infants often manifest sleepiness, limp muscle tone, and poor suck reflex (Sullivan & Berman, 2000; Mofenson & Caraccio, 1991). Lethargy and hypotonia were two early symptoms reported in two premature infants that received inadvertent excessive doses of magnesium via total parenteral nutrition (Ali et al, 2003).
c) CASE REPORT (ADULT): Following an infusion of 24.7 grams of magnesium sulfate, a 29-year-old woman became rapidly comatose and apneic (Fletcher & Parr, 2000).
d) CASE REPORT: A 31-year-old woman with normal renal function developed severe hypermagnesemia (magnesium level 9.8 mmol/L (23.6 mg/dL)) following chronic gargling with Epsom salt for halitosis. She experienced coma, hypotension, acute renal failure, and multiple episodes of asystole and ventricular fibrillation requiring repeated defibrillation. Despite intensive care, including hemodialysis, she died of a cardiac arrest (Birrer et al, 2002).
e) CASE REPORT: A 16-year-old girl who received a bone marrow transplant 45 days before presentation, developed hypermagnesemia (magnesium level 5.9 mmol/L) resulting in hypotension, hypothermia, and coma after ingesting 15 mL of magnesium-containing antacid every 2 hours instead of 4 times daily. Following supportive care, she recovered completely (Jaing et al, 2002).
f) CASE REPORT: A 65-year-old man with a history of colon adenocarcinoma who was admitted for management of hypokalemia and hypomagnesemia secondary to diarrhea, developed lightheadedness, a heavy feeling in his arms, slurred speech, and a reduced Glasgow Coma Scale score of 12/15 after receiving IV infusions of potassium chloride and magnesium sulfate. No hemorrhage or evidence of acute ischemic injury was observed in a CT scan of the head. Laboratory results revealed an elevated magnesium concentration (3.55 mmol/L). At this time, it was determined that the magnesium infusion was inadvertently prepared using 50 mL (five 10 mL ampoules) of magnesium sulfate 50% (2 mmol/mL) instead of 6 mL of magnesium sulfate 50% (100 mmol [25 g of magnesium IV over about 2 hours instead of the prescribed 12 mmol [3 g]). He recovered gradually over the next 6 hours following supportive care. His magnesium concentrations 10 hours after the overdose and the following day were 1.57 mmol/L and 0.86 mmol/L, respectively (Cavell et al, 2015).

B) HYPOREFLEXIA

1) WITH POISONING/EXPOSURE

a) LOSS OF REFLEXES: Loss of deep tendon reflexes (Mg level 5 mEq/L) usually precedes respiratory depression (Mg level 10 mEq/L) and provides a useful clinical monitor in the therapeutic or overdose setting (Zwanger, 1986). Hypermagnesemia causes neuromuscular blockade by inhibiting the release of presynaptic acetylcholine, which results in flaccid paralysis and respiratory depression. Hyporeflexia is an indicator of severe hypermagnesemia and a predictor of cardiac and respiratory toxicity (Razavi & Somers, 2000).
b) CASE REPORT: Areflexia and bilateral Babinski's signs, quadriplegia, and facial diplegia were noted in a diabetic woman with a serum magnesium level of 8.4 mg/dL (Castelbaum et al, 1989).
c) CASE REPORT: Another woman who was inadvertently administered 2 mL of 50% magnesium sulfate intrathecally suffered paralysis of her legs with no loss of sensation (Lejuste, 1985).
d) CASE REPORT: Flaccidity with hypotonia and no Babinski reflex was reported in all extremities in a female after ingestion of 50 grams of Epsom salts (400 mEq magnesium) (Qureshi & Melonakos, 1996).
e) CASE REPORT/INFANT: Hypermagnesemia (3.9 mmol/L; normal 0.6-0.8 mmol/L) with lethargy and hypotonia was reported in a 4-week-old infant following administration of 1 teaspoonful daily of milk of magnesia for one week prior to admission. The infant improved after 4 days with lowered serum magnesium and was then discharged (Sullivan & Berman, 2000).
f) CASE REPORT: Diffuse motor weakness and altered mental status were reported in a 47-year-old female within 30 minutes following the ingestion of 4 tablespoonfuls of Epsom salt (magnesium sulfate 140 mEq/17.5 grams). Deep tendon reflexes were absent. Magnesium serum concentration of 18.3 mEq/L was noted. The patient improved following fluid hydration with normal saline. She was discharged to home 2 days after admission with a serum Mg of 2.3 mEq/L (Nordt et al, 1996).

C) PARALYSIS

1) WITH POISONING/EXPOSURE

a) At magnesium serum concentrations at or greater than 10 mEq/L, paralysis of voluntary muscles and areflexia occurs (Razavi & Somers, 2000).

D) SEIZURE

1) WITH POISONING/EXPOSURE

a) Excessive absorption of magnesium from cathartics may result in CNS depression and seizures, most notably in renal failure patients.

E) TETRAPARESIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Severe hypermagnesemia (10.58 mg/dL (4.35 mmol/L) on day 10) and quadriparesis were reported in a woman with end-stage renal disease and on continuous ambulatory peritoneal dialysis (CAPD) after ingesting magnesium-containing laxatives (magnesium oxide powder 3 g/day) for approximately 1 year. On day 8, her muscle strength was symmetrically reduced to grade 1-2 in all extremities. Nerve conduction velocity revealed severe polyneuropathy with blocked nerve conduction. Following supportive therapy, her serum magnesium concentration decreased to 3.1 mg/dL (1.27 mmol/L) on day 28 and her symptoms improved gradually (Jung et al, 2008).

Gastrointestinal

3.8.2)

A) VOMITING

1) WITH THERAPEUTIC USE

a) Nausea and vomiting may commonly occur with hypermagnesemia and are early symptoms (Kutsal et al, 2007; Wilson et al, 1986) Bruhwiler et al, 1994).

B) DRUG-INDUCED ILEUS

1) WITH POISONING/EXPOSURE

a) Magnesium toxicity may rarely result in paralytic ileus. Razavi & Somers (2000) reported a 71-year-old patient with hypermagnesemia-induced multiorgan failure, which included a paralytic ileus. Other factors which may have contributed to the ileus were hyponatremia and metabolic alkalosis (Razavi & Somers, 2000).

C) PERFORATION OF INTESTINE

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Bowel perforation and subsequent peritonitis led to death in a 55-year-old woman given aggressive cathartic therapy for treatment of aspirin overdose. She received 4 doses of magnesium sulfate (total 120 grams) and 6 doses of sorbitol (total amount unspecified) (Brent et al, 1989).

D) OBSTRUCTION OF COLON

1) WITH THERAPEUTIC USE

a) CASE REPORT: A 33-year-old pregnant woman (33-4/7 week with twin gestation) developed recurrent acute colonic pseudo-obstruction (Ogilvie's syndrome) after receiving intravenous magnesium (a 6 gram bolus and then 3 to 4 g/hr) and nifedipine (20 mg every 4 hours, decreased to 20 mg every 6 hours) for preterm labor. Abdominal radiograph showed massive transverse and sigmoid colon dilation requiring colonoscopic decompression. Mucosal exudates and changes consistent with ischemic mucosa were observed from the proximal transverse colon to the hepatic flexure. Magnesium and nifedipine were discontinued and repeated colonoscopies were needed to manage the recurrent colonic dilations before the delivery of healthy twins (Pecha & Danilewitz, 1996).

Genitourinary

3.10.2)

A) RENAL FAILURE SYNDROME

1) WITH THERAPEUTIC USE

a) Hypermagnesemia may contribute to renal insufficiency in patients with no prior history of renal dysfunction (Birrer et al, 2002; Razavi & Somers, 2000). Patients with preexisting renal insufficiency are predisposed to develop hypermagnesemia due to reduced magnesium elimination.
b) Progression of renal failure was associated with hypermagnesemia during Renacidin irrigation of a kidney to attempt to dissolve the calyceal/papillary calcification and provide symptomatic relief in a 7-year-old with nephrocalcinosis (Wilson et al, 1986).

Dermatologic

3.14.2)

A) FLUSHING

1) WITH POISONING/EXPOSURE

a) Cutaneous flushing may be noted (Zwanger, 1986).

B) SKIN ULCER

1) WITH POISONING/EXPOSURE

a) Magnesium particles embedded in the skin may cause local swelling, vesiculation, necrosis and ulceration. Slow-healing skin blebs characterized by gas development ("chemical gas gangrene") and lymphangitis may develop.

Musculoskeletal

3.15.2)

A) HYPOREFLEXIA

1) WITH POISONING/EXPOSURE

a) LOSS OF REFLEXES: Loss of deep tendon reflexes usually precedes respiratory depression and provides a useful clinical monitor in the therapeutic or overdose setting (Zwanger, 1986).

B) OSTEOPENIA

1) WITH THERAPEUTIC USE

a) Chronic Intrauterine Exposure

1) SKELETAL DEMINERALIZATION AND FRACTURES: Multiple fractures and severe osteopenia were reported in infant triplets who were chronically exposed to magnesium sulfate in utero. The mother went into preterm labor at 22 weeks gestation and was treated with terbutaline, sulindac, indomethacin, and magnesium sulfate (IV 2 to 2.5 g/hr) for 8.5 weeks until birth at 30 weeks gestation. Large fontanelles, widely split sutures, and craniotabes were noted in the 3 infants. Thin demineralized ribs and humeri were noted on chest x-ray. One infant died on the second day of life from E. coli sepsis. Fractures of the humeri, radii, ulnae, and tibiae, with deformities of the femurs were noted on day 20 after birth in the 2 surviving infants. At 18 months, there were no signs of bone abnormalities or deformities in the two surviving infants (Wedig et al, 2006).

Reproductive

3.20.1)

A) Magnesium sulfate is classified as FDA pregnancy category A . Magnesium sulfate and the citric acid, magnesium oxide, and sodium picosulfate combination are classified as FDA pregnancy category B.

3.20.2)

A) ANIMAL STUDIES

1) Magnesium, given as the chloride hexahydrate, produced no teratogenic effects in rats exposed at up to 800 mg/kg/day (Usami et al, 1996).
2) Magnesium is required for normal reproduction in experimental animals and (presumably) humans. Magnesium DEFICIENCY caused resorptions (Gunther, 1973) and birth defects (pp 481-492; Hurley & Cosens, 1970) in rats. Prenatal magnesium deficiency affected the central nervous system and caused a characteristic staggering in rats (Hurley, 1958), guinea pigs (Everson, 1959), cattle (Dyer, 1964), and mice (Erway, 1966). Magnesium deficiency caused prenatal death, but was not teratogenic in pigs (Plumlee, 1956).
3) Magnesium sulfate reduced fetal cerebral blood flow and increased fetal death in sheep when injected following maternal hemorrhage (Reynolds et al, 1996).

3.20.3)

A) PREGNANCY CATEGORY

1) Magnesium sulfate is classified as FDA pregnancy category D (U.S. Food and Drug Administration (FDA), 2013). Magnesium sulfate and the citric acid, magnesium oxide, and sodium picosulfate combination are classified as FDA pregnancy category B (Prod Info PREPOPIK(TM) oral solution, 2012).

B) BONE CHANGES

1) The FDA advises against long term use (greater than 5 to 7 days) of magnesium sulfate when used to stop preterm labor, due to the risk of low calcium levels and bone changes in exposed infants (U.S. Food and Drug Administration (FDA), 2013).
2) OSTEOPENIA

a) Multiple fractures and severe osteopenia were reported in infant triplets who were chronically exposed to magnesium sulfate in utero. The mother went into preterm labor at 22 weeks gestation and was treated with terbutaline, sulindac, indomethacin, and magnesium sulfate (IV 2 to 2.5 grams/hour) for 8.5 weeks until birth at 30 weeks gestation. Large fontanelles, widely split sutures, and craniotabes were noted in the three infants. Thin demineralized ribs and humeri were noted on chest x-ray. One infant died on the second day of life from E. coli sepsis. Fractures of the humeri, radii, ulnae, and tibiae, with deformities of the femurs were noted on day 20 after birth in the two surviving infants. At 18 months, there were no signs of bone abnormalities or deformities in the two surviving infants (Wedig et al, 2006).

C) ABORTION

1) CASE REPORT: A 23-year-old woman, 22 weeks pregnant, suffered paralysis of her legs and later miscarried after receiving 2 milliliters 50 percent magnesium sulphate intrathecally. The authors concluded that the miscarriage was not due to the magnesium since the patient had recovered from neural deficits; however, no conclusive evidence exists (Lejuste, 1985).

D) INTESTINAL PERFORATION

1) Higher antenatal doses of magnesium sulfate (100 g or more) were associated with higher risks of spontaneous intestinal perforation and death in extremely low birthweight infants (less than 1000 g), particularly those delivered at less than 25 weeks of gestation (Rattray et al, 2014).

E) DEATH

1) Higher antenatal doses of magnesium sulfate (100 g or more) were associated with higher risks of spontaneous intestinal perforation and death in extremely low birthweight infants (less than 1000 g), particularly those delivered at less than 25 weeks of gestation (Rattray et al, 2014).
2) High dose (greater than 48 grams) tocolytic magnesium sulfate therapy was reported to be associated with increased perinatal mortality among fetuses and neonates weighing 700 to 1249 grams in a case-control study (n=127). Out of 18 deaths, 4 were fetal deaths and 14 were neonatal deaths (Scudiero et al, 2000).

F) PLACENTAL BARRIER

1) Magnesium levels in umbilical venous serum were slightly higher than in the umbilical artery; pregnant women had 20% lower serum magnesium levels than did nonpregnant women. Fetal blood levels of ionized magnesium are comparable to those of the mother (Handwerker et al, 1993; Mason et al, 1996).
2) When magnesium sulfate was given intravenously to stop premature uterine contractions, magnesium concentrations were elevated in fetal serum within one hour and levels were increased in amniotic fluid within 3 hours (Hallak et al, 1993).

G) MATERNAL OVERDOSE AND FETAL DISTRESS

1) CASE REPORT: A 36-year-old pregnant woman at 32 weeks gestation with a diagnosis of preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, underwent an emergent cesarean delivery under general anesthesia and delivered a live male infant with Apgar scores of 4 and 8 at 1 and 5 minutes, respectively. Because of suboptimal uterine tone noted about 10 minutes after delivery, the obstetrician requested an increase in the rate of the oxytocin infusion from 125 mL/hr to 240 mL/hr. However, the anesthetist inadvertently increased the magnesium infusion from 12.5 mL/hr to 240 mL/hr. After surgery was completed, there were no signs of arousal and tidal volume was only 30 mL. At this time, magnesium toxicity was considered and it was estimated that the patient had received about 13 g of magnesium over 40 minutes. An ECG showed markedly peaked T-waves. Following supportive care, including the administration of 10 mL of IV 10% calcium gluconate, her tidal volume increased to about 250 mL and she opened her eyes to command. Since she still had an erratic respiratory pattern and could not move her limbs or fingers, she was re-sedated and given another 10 mL bolus of 10% calcium gluconate, normal saline 1 L, furosemide 20 mg, and a dextrose-insulin infusion (human Actrapid 10 units in 50 mL of 50% glucose over 1 hours). Her condition improved within 30 minutes of the dextrose-insulin infusion as observed by her ECG and normalizing respiratory pattern. Her condition continued to improve over the next few days and she was discharged on day 5. Her infant underwent invasive ventilation, and was discharged after 34 days of hospitalization in good condition (McDonnell et al, 2010).

H) ECLAMPSIA

1) Serum magnesium concentrations were not different in pregnant women with pre-eclampsia and normal pregnant women; intracellular magnesium concentrations in erythrocytes were significantly lower in pre-eclamptic women (Kisters et al, 1993).
2) Magnesium supplementation was effective in decreasing blood pressure in women with pregnancy-induced hypertension; infants born to women administered magnesium sulfate had higher birth weights than infants born to women with gestational hypertension who had not received magnesium sulfate (Rudnicki et al, 1991).
3) Magnesium sulfate given in a single oral or intravenous dose was effective in lowering systemic vascular resistance and increasing the cardiac index in preeclamptic patients at approximately the 32nd week of pregnancy; it had no effect in women in premature labor (Scardo et al, 1995). Magnesium sulfate decreased cerebral vasospasm in preeclamptic women and was more effective than phenytoin for prevention of eclamptic seizures (Naidu et al, 1996).
4) Magnesium DEFICIENCY may be involved in eclampsia, gestational diabetes, acute fatty liver, and coagulation defects during pregnancy (Newman & Amarasingham, 1993).

I) BLEEDING TIME INCREASED

1) A single magnesium sulfate bolus prolonged the bleeding time in normotensive and hypertensive pregnant women (Fuentes et al, 1995).

J) LACK OF EFFECT

1) A case-control comparison study showed that magnesium sulfate tocolysis was not associated with increased neonatal mortality rates in premature infants (Grether et al, 1998).

K) ANIMAL STUDIES

1) MAGNESIUM OXIDE, CITRIC ACID, AND SODIUM PICOSULFATE COMBINATION

a) Oral doses of the combination up to 2000 mg/kg/day (about 1.2 times the recommended human dose based on the body surface area) in pregnant rats did not result in any harm to the fetus or any adverse effect on pre and postnatal development. In rabbits, treatment-related mortalities were observed at all doses, however, the reproduction study was not adequate (Prod Info PREPOPIK(TM) oral solution, 2012).

3.20.4)

A) LACK OF INFORMATION

1) MAGNESIUM OXIDE, CITRIC ACID, AND SODIUM PICOSULFATE COMBINATION

a) It is unknown whether the citric acid, magnesium oxide, and sodium picosulfate combination is excreted in human milk (Prod Info PREPOPIK(TM) oral solution, 2012).

B) MAGNESIUM SULFATE

1) Magnesium sulfate levels in human milk are elevated in women taking supplemental magnesium sulfate. In preeclamptic women administered 1 gram magnesium sulfate IV every hour during the first 24 hours after delivery, magnesium levels in breast milk averaged 64 mcg/mL, as compared to nontreated controls with breast milk levels averaging 48 mcg/mL (Briggs et al, 1998).

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS7439-95-4 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

3.21.2)

A) At the time of this review, no studies were found on the potential carcinogenic activity of magnesium in humans or experimental animals.

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Monitor vital signs.
B) Monitor deep tendon reflexes (hyporeflexia generally precedes more severe toxicity), and monitor for CNS and respiratory depression.
C) Monitor serum electrolytes, renal function, and serial magnesium concentrations after significant exposure.
D) Obtain an ECG and institute continuous cardiac monitoring in symptomatic patients.
E) Normal serum magnesium concentrations are 1.5 to 2.5 mEq/L. At a magnesium concentrations of 3 mEq/L, patients may experience nausea and vomiting. At a concentration of 4 mEq/L, patients may have drowsiness, sweating, and unsteadiness. At 5 mEq, ECG may show QRS widening and PR prolongation. At concentrations of 6 to 7 mEq/L bradycardia and hypotension may develop. Finally, at concentrations of 10 to 15 mEq/L, voluntary muscle paralysis, heart block, and respiratory paralysis may develop.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) Rapid serum magnesium estimation is widely available; the normal range is 1.5 to 2.5 mEq/L of serum (Baselt, 2000).
2) Free Mg2+ ion is held within a narrow range of 0.53 to 0.67 mmol/L (1.06 to 1.34 mEq/L), while total magnesium can vary between 0.70 and 0.96 mmol/L (1.4 to 1.92 mEq/L). The ratio of free:total magnesium is usually approximately 71%, but can vary widely between individuals (Altura et al, 1994).
3) Magnesium deficiency may be present in the face of normal serum magnesium but low serum levels usually imply magnesium deficiency. Clinical correlates of serum levels have been detailed by Randall et al (1964) (Randall et al, 1964) and Razavi & Somers (2000) (Razavi & Somers, 2000):

SERUM MAGNESIUM
EFFECT	LEVEL (mEq/L)
Nausea and Vomiting	3 to 8
Drowsiness; hyporeflexia	greater than 4
Decreased DT reflexes, ECG changes (including an increased P-R interval and QRS duration, and an increased height of T wave)	greater than 5
Somnolence; hypotension	6 to 7
Paralysis of voluntary muscles; areflexia	10
Respiratory depression, coma	10 to 14
Cardiac arrest	15 to 16

4.1.3)

A) URINARY LEVELS

1) Magnesium found in normal urine ranges from 2 to 4 mEq/L (1 to 6 mmol/L) (Baselt, 2000).
2) A 24-hour urine specimen is important to assess magnesium excretion accurately due to circadian variation (Elin, 1987).

4.1.4)

A) OTHER

1) ECG

a) Obtain an ECG and institute continuous cardiac monitoring for all symptomatic patients or patients with elevated serum magnesium concentrations.

Methods

A)

1) Serum magnesium has been determined by colorimetry, emission spectrometry, and fluorometry. Less interference has been reported with atomic absorption spectrometry and it may be useful for urine specimens (Baselt, 2000).
2) Magnesium is usually determined in serum rather than plasma, because anticoagulants for plasma can be contaminated with magnesium (Elin, 1987).
3) While mononuclear blood cell magnesium is a better predictor of total body magnesium status, serum magnesium levels are more readily available and useful in assessing acute toxicity (Elin, 1987).
4) An ion-selective electrode for magnesium gave accurate readings for FREE magnesium in whole blood, serum or plasma. Results were in strict agreement with those from atomic absorption spectroscopy (Altura et al, 1994).
5) Magnesium hair concentrations were measured by atomic absorption spectrophotometry, with a detection limit of 4 micromols/liter (equivalent to 0.4 micromols/gram of hair) (Solarska et al, 1995).

Treatment

Life Support

A)

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients with persistent weakness or magnesium concentrations that are not declining despite hydration should be admitted. Patients with hypotension, ECG changes, CNS or respiratory depression should be admitted to an ICU setting. Patients should remain admitted until symptoms are clearly improving and clinically stable.

6.3.1.2) HOME CRITERIA/ORAL

A) Patients who are asymptomatic and exposures within therapeutic range may stay at home. Patients with minimal symptoms that are improving may also be monitored at home.

6.3.1.3) CONSULT CRITERIA/ORAL

A) Consult a medical toxicologist or poison center for any patient with severe toxicity or in whom the diagnosis is unclear. Consult a nephrologist for hemodialysis in patients with severe toxicity. Patients with severe toxicity or renal insufficiency may require transfer to a hospital that can perform emergent hemodialysis.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Patients with systemic or moderate to severe symptoms should be sent to a healthcare facility for observation until symptoms are clearly improving and the patient is clinically stable.

Monitoring

A)

B)

C)

D)

E)

Oral Exposure

6.5.1)

A) PREHOSPITAL: Gastrointestinal decontamination is not indicated as activated charcoal does not bind to magnesium. Wash exposed skin with soap and water; irrigate exposed eyes.

6.5.2)

A) ACTIVATED CHARCOAL

1) Gastrointestinal decontamination is not indicated as activated charcoal does not bind magnesium.

6.5.3)

A) MONITORING OF PATIENT

1) Monitor vital signs.
2) Monitor deep tendon reflexes (hyporeflexia generally precedes more severe toxicity), and monitor for CNS and respiratory depression.
3) Monitor serum electrolytes, renal function, and serial magnesium concentrations after significant exposure.
4) Obtain an ECG and institute continuous cardiac monitoring in symptomatic patients.
5) Normal serum magnesium concentrations are 1.5 to 2.5 mEq/L. At a magnesium concentrations of 3 mEq/L, patients may experience nausea and vomiting. At a concentration of 4 mEq/L, patients may have drowsiness, sweating, and unsteadiness. At 5 mEq, ECG may show QRS widening and PR prolongation. At concentrations of 6 to 7 mEq/L bradycardia and hypotension may develop. Finally, at concentrations of 10 to 15 mEq/L, voluntary muscle paralysis, heart block, and respiratory paralysis may develop.

B) CALCIUM

1) Calcium salts will somewhat antagonize respiratory depression induced by hypermagnesemia, presumably by displacing magnesium from cell membranes.
2) In severe toxicity, calcium may be used to temporarily improve symptoms until more definitive therapy (hemodialysis) can be instituted.
3) DOSE: Administer IV calcium chloride 10% (DOSE: 0.2 to 0.5 mL/kg/dose up to 10 mL/dose over 5 to 10 minutes). Repeat dose as needed. Monitor ECG and stop infusion if heart rate begins to decrease.

C) INSULIN

1) DEXTROSE/INSULIN INFUSION: One study recommended the use of a dextrose-insulin infusion in patients with cardiac toxicity after magnesium overdose (McDonnell et al, 2010).

a) CASE REPORT: A 36-year-old pregnant woman at 32 weeks gestation with a diagnosis of preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, underwent an emergent cesarean delivery under general anesthesia and delivered a live male infant with Apgar scores of 4 and 8 at 1 and 5 minutes, respectively. Because of suboptimal uterine tone noted about 10 minutes after delivery, the obstetrician requested an increase in the rate of the oxytocin infusion from 125 mL/hr to 240 mL/hr. However, the anesthetist inadvertently increased the magnesium infusion from 12.5 mL/hr to 240 mL/hr. After surgery was completed, there were no signs of arousal and tidal volume was only 30 mL. At this time, magnesium toxicity was considered and it was estimated that the patient had received about 13 g of magnesium over 40 minutes. An ECG showed markedly peaked T-waves. Following supportive care, including the administration of 10 mL of IV 10% calcium gluconate, her tidal volume increased to about 250 mL and she opened her eyes to command. Since she still had an erratic respiratory pattern and could not move her limbs or fingers, she was re-sedated and given another 10 mL bolus of 10% calcium gluconate, normal saline 1 L, furosemide 20 mg, and a dextrose-insulin infusion (human Actrapid 10 units in 50 mL of 50% glucose over 1 hours). Her condition improved within 30 minutes of the dextrose-insulin infusion as observed by her ECG and normalizing respiratory pattern. Her condition continued to improve over the next few days and she was discharged on day 5. Her infant underwent invasive ventilation, and was discharged after 34 days of hospitalization in good condition (McDonnell et al, 2010).

D) HYPOTENSIVE EPISODE

1) SUMMARY

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

2) DOPAMINE

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

3) NOREPINEPHRINE

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

E) HYPOTHERMIA

1) Patients with severe hypothermia should be placed under a warming blanket or use a "hugg-bear" or equivalent device.

Enhanced Elimination

A)

1) Hemodialysis is the most effective method to remove significant quantities of magnesium and may reverse life-threatening symptoms within 30 minutes. Emergent dialysis should be considered in any patients with severe toxicity (hypotension, dysrhythmias, severe CNS depression, respiratory depression) or patients with moderate effects and severe renal insufficiency.

B)

1) Hemodialysis is the most effective method to remove significant quantities of magnesium. Respiratory depression, coma, and hypotension have reversed within 30 minutes of institution of dialysis (Ferdinandus et al, 1981).
2) Dialysis decreased the serum magnesium from 5.1 milliequivalents/liter in approximately four hours in one adult patient (Jones et al, 1986).
3) CASE REPORT: A 32-year-old woman with postpartum eclampsia and renal insufficiency (serum creatinine 4.78 mg/dL) developed toxic hypermagnesemia (serum magnesium 15.4 mg/dL) after receiving intravenous magnesium sulfate (2-g bolus, 1 g/hr continuously). Because of cardiopulmonary failure and failure of calcium chloride therapy, she underwent hemodialysis. Following 13 hours of hemodialysis, her serum magnesium decreased to 6.5 mg/dL, and gradually decreased further after the cessation of hemodialysis (Hirose et al, 2002).
4) CASE REPORT: A 14-year-old girl with severe constipation and ileus and without preexisting renal dysfunction presented with lethargy and hypotension (BP 70/40 mm Hg) after receiving 18 g/day of magnesium hydroxide-containing cathartic for 7 days. Serum magnesium concentration was elevated at 14.9 mg/dL with a low ionized calcium 1.06 mg/dL. She experienced bradycardia (30 beats/min) and respiratory arrest one hour later. She was treated with emergent hemodialysis, with reduction of her serum magnesium concentration to 6.9 mg/dL after 2 hours of dialysis. Serum magnesium concentration rebounded to 7.9 mg/dL, and a second hemodialysis treatment was performed; she made a full recovery and was discharged without recurrence of hypermagnesemia (Kutsal et al, 2007).

C)

1) Diuresis will promote renal excretion of magnesium in mildly intoxicated patients with intact renal function, but has not been shown to be effective in severely symptomatic patients or those with renal insufficiency.

a) In a 35-year-old man with mild chronic renal failure, 24 hours was required to reverse symptoms of coma and respiratory depression using calcium and diuresis (Jenny et al, 1978).

Abstracts

Case Reports

A)

1) A 39-year-old woman admitted following a large ingestion of a tricyclic antidepressant received repeated doses of activated charcoal and magnesium citrate which resulted in an increase in serum magnesium levels followed by acute neuromuscular deterioration and respiratory depression. The patient was treated with dialysis, and improved slowly without complications (Jones et al, 1986).
2) Symptomatic hypermagnesemia (respiratory arrest, somnolence, AV block, serum magnesium 13.2 mEq/L) was described in a 50-year-old man with normal renal function. He was administered 100 grams of magnesium sulfate every 4 hours in combination with activated charcoal. The total magnesium received was 90 grams (7,380 mEq) (Fassler et al, 1985).
3) Hypermagnesemia resulted from ingestion of 200 grams of magnesium sulfate in a 25-year-old woman with normal renal function. Coma and hypothermia were present, but no respiratory or cardiovascular signs occurred (Garcia-Webb et al, 1984).
4) Cardiopulmonary arrest and severe hypermagnesemia were reported in a 56-year-old woman who overdosed on multiple drugs and received multiple dose charcoal combined with 75 grams per hour of magnesium sulfate for 6 doses.

a) The initial serum magnesium level was 21.3 mEq/L which declined without treatment (Smilkstein et al, 1988).

5) Two patients were treated with magnesium sulfate enemas for hepatic encephalopathy. Magnesium was measured for nutritional assessment (12.2 mg/dL and 35.5 mg/dL). Hypercalcemia, raised phosphate concentrations, and renal failure were also reported (Collinson & Burroughs, 1986).
6) Three patients with serum magnesium levels of 19.6, 32, and 10.8 mg/dL, respectively, developed loss of deep tendon reflexes following ingestion of Dead Sea water. Lack of cardiac effects was attributed to concurrent hypercalcemia (16, 19.7, and 15.6 mg/dL). All 3 patients were hemodialyzed and rapid correction of calcium and magnesium concentrations were reported (Oren et al, 1987).
7) A 55-year-old man ingested 3 tablespoonfuls of magnesium sulfate and subsequently developed coma 2 hours later. Upon admission he was given 17.45 grams of magnesium citrate by nasogastric tube along with activated charcoal. The initial serum magnesium was 9.5 mmol/L (19 mEq/L). After diuresis and supportive therapy, the patient regained consciousness 4 hours post-admission. It was estimated that the patient had ingested 750 mmol of magnesium sulfate and 81 mmol of magnesium citrate (Gerard et al, 1988).
8) An 87-year-old man with acute-on-chronic theophylline toxicity received multiple dose activated charcoal and 4 ounces of magnesium citrate with every other dose, for a total of 5 doses. A serum magnesium level of 5.3 mg/dL was associated with decreased deep tendon reflexes and confusion (Garrelts et al, 1989).
9) A 55-year-old woman received magnesium sulfate 120 grams and 6 doses of sorbitol, along with activated charcoal, for treatment of an aspirin overdose. She became hypotensive and bradycardic with a magnesium level of 17.8 mEq/L 24 hours after admission. She stabilized after dialysis until the following day, when she developed an acute abdomen and died. Bowel perforation was documented at postmortem examination (Brent et al, 1989).
10) Three patients exhibited signs of hypermagnesemia after being accidentally given large doses of 50% magnesium sulfate.

a) All patients had levels of 4.8 mmol/L or higher. Dosing errors were due to mistaken interpretation of the quantity of an "amp" and mistaken identity of labels on vials (Hoffman et al, 1989).

11) A pregnant woman at 32 weeks gestation inadvertently received 30 grams of intravenous magnesium sulfate over a few minutes. She quickly became unresponsive to pain and then became cyanotic and apneic, with bradycardia and no measurable peripheral pulse. She was treated with oxygen, calcium gluconate, forced diuresis and recovered (Bruhwiler et al, 1994). Magnesium level immediately after the event was 7.4 mmol/L. There were no apparent adverse effects in the children (Bruhwiler et al, 1994).

Range Of Toxicity

Workplace Standards

A)

1) Not Listed

B)

1) Not Listed

C)

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

D)

1) Not Listed

Toxicity Information

7.7.1)

A) MAGNESIUM SULFATE

1) LD50- (INTRAPERITONEAL)MOUSE:

a) 1029 mg/kg (RTECS , 2001)

2) LD50- (SUBCUTANEOUS)MOUSE:

a) 645 mg/kg (RTECS , 2001)

3) LD50- (SUBCUTANEOUS)RAT:

a) 1200 mg/kg (RTECS , 2001)

Summary

A)

B)

C)

D)

E)

F)

G)

Therapeutic Dose

7.2.1)

A) DIETARY SUPPLEMENT

1) 27 to 54 mg 2 or 3 times per day
2) 100 mg 4 times per day
3) 133 mg 3 times per day

B) MAGNESIUM CITRATE

1) CONSTIPATION: 6.5 to 10 ounces ORALLY as a single or divided dose in 24 hours (Prod Info Citroma(R) oral liquid, 2011)
2) HYPOMAGNESEMIA: 400 mg ORALLY daily with meals (Prod Info magnesium citrate tablets, 2006).

C) MAGNESIUM HYDROXIDE

1) CHEWABLE TABLETS: 2 to 4 chewable tablets (311 mg each) taken every 4 hours up to 4 times daily; MAX: 8 tablets/day. Each tablet contains 130 mg of elemental magnesium (Prod Info PHILLIPS'(R) chewable oral tablets, 2005)

D) MAGNESIUM SULFATE

1) TORSADES DE POINTES

a) 1 to 2 g diluted in 10 mL D5W IV/intraosseous over 15 minutes (Neumar et al, 2010)

2) HYDROFLUORIC ACID INGESTION

a) Give initial magnesium sulfate intravenous bolus of 2 to 4 grams. Maintenance infusion is 1 to 2 grams/hour, although higher rates may be necessary if ECG evidence of hypocalcemia persists. Continue infusion for 1 to 2 hours and then taper slowly while monitoring ECG for evidence of QT interval prolongation. Follow serum calcium levels (Goldfrank et al, 1998). Magnesium sulfate is used to prevent hypocalcemia and ventricular dysrhythmia following a hydrogen fluoride exposure.

3) ECLAMPSIA

a) Initial, 4 to 5 g in 250 mL of D5W or NS given IV AND simultaneous IM doses of up to 10 g of undiluted 50% magnesium sulfate solution (5 g in each buttock) (Prod Info magnesium sulfate heptahydrate IV, IM injection, solution, 2009)
b) Initial (alternative), dilute 4 g dose (50% magnesium sulfate solution to a 10% or 20% solution) and give IV over 3 to 4 minutes (Prod Info magnesium sulfate heptahydrate IV, IM injection, solution, 2009)
c) Maintenance, 1 to 2 g/hr IV until paroxysms cease OR 4 to 5 g IM into alternate buttocks every 4 hours as needed; MAX daily dose is 30 to 40 g (Prod Info magnesium sulfate heptahydrate IV, IM injection, solution, 2009)

4) HYPOMAGNESEMIA

a) mild hypomagnesemia, 1 g (magnesium sulfate 50% solution; 8.12 mEq) IM every 6 hours for 4 doses (Prod Info magnesium sulfate heptahydrate IV, IM injection, solution, 2009)
b) severe hypomagnesemia, up to 250 mg/kg (magnesium sulfate 50% solution) IM in 4 hours OR 5 g (40 mEq) in 1 L of D5W or NS by slow IV infusion over 3 hours (Prod Info magnesium sulfate heptahydrate IV, IM injection, solution, 2009)
c) TPN, maintenance, 1 to 3 g (8 to 24 mEq) magnesium sulfate daily given parenterally (Prod Info magnesium sulfate heptahydrate IV, IM injection, solution, 2009)

5) ANALGESIA

a) Several studies have used intrathecal or epidural magnesium sulfate (50 to 100 mg) in combination with opioids to improve postoperative analgesia and reduce the need for postoperative analgesic use. It is suggested that magnesium sulfate produces anti-nociception and increases opioid activity, by its action as a voltage-gated N-methyl-D-aspartate (NMDA) receptor agonist; however, magnesium sulfate does not have any primary analgesic effect when used alone (Khalili et al, 2011; Mebazaa et al, 2011).

1) In one study, the combination of 100 mg intrathecal magnesium sulfate and 15 mg of bupivacaine without any opioid use, increased the duration of sensory block, reduced postoperative analgesic consumption, and significantly prolonged the onset of spinal anesthesia in patients undergoing lower extremity surgery (Khalili et al, 2011).

7.2.2)

A) MAGNESIUM CITRATE

1) CONSTIPATION: 2 to under 6 years of age, 2 to 3 ounces ORALLY, as a single or divided dose; MAX 3 ounces in 24 hours (Prod Info Citroma(R) oral liquid, 2011)
2) CONSTIPATION: 6 to under 12 years of age, 3 to 7 ounces ORALLY as a single or divided dose in 24 hour (Prod Info Citroma(R) oral liquid, 2011)
3) CONSTIPATION: 12 years and older, 6.5 to 10 ounces ORALLY as a single or divided dose in 24 hour (Prod Info Citroma(R) oral liquid, 2011)

B) MAGNESIUM SULFATE

1) TORSADES DE POINTES

a) 25 to 50 mg/kg IV/intraosseous rapid infusion (over several minutes); MAX dose 2 g (Kleinman et al, 2010)

2) HYPOMAGNESEMIA

a) TPN, maintenance, infants, 0.25 to 1.25 g (2 to 10 mEq) magnesium sulfate daily given parenterally (Prod Info magnesium sulfate heptahydrate IV, IM injection, solution, 2009)
b) hypomagnesemia, pediatrics, 25 to 50 mg/kg IV infusion over 30 to 60 minutes; repeat dose as necessary; max 2 g/dose (Kleinman et al, 2010; Manrique et al, 2010; Haque & Saleem, 2009)
c) hypomagnesemia, neonates, 25 to 50 mg/kg IV infusion over 30 to 60 minutes; repeat dose as necessary (Kleinman et al, 2010; Manrique et al, 2010; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008)

Minimum Lethal Exposure

A)

1) Death secondary to bowel perforation was reported in a 55-year-old woman following administration of 120 grams of magnesium sulfate and 6 doses of sorbitol for treatment of an aspirin overdose (Brent et al, 1989).
2) Accidental IV bolus injection of 20 grams of magnesium sulfate instead of 2 grams, for alcohol withdrawal, resulted in cardiac arrest in 2 males. One patient recovered and the other died 3 days later (Vissers & Purssell, 1995).
3) Fatal hypermagnesemia from mega-mineral and dietary supplements was reported in 2 children. One child was resuscitated from cardiac arrest but then died within 24 hours following persistent bradycardia and heart block (McGuire et al, 2000; Kulkarni et al, 1999).

Maximum Tolerated Exposure

A)

B)

1) MULTIPLE DOSE ACTIVATED CHARCOAL/MAGNESIUM SULFATE

a) Elevated serum magnesium levels can occur in overdose patients with normal renal function following as few as 3 doses of 30 grams of magnesium sulfate every 4 hours as part of a multiple-dose activated charcoal/cathartic regimen (Smilkstein et al, 1988a).
b) A single 30 gram magnesium sulfate dose did not produce elevated serum magnesium levels in this same setting (Smilkstein et al, 1988a).
c) Symptomatic hypermagnesemia has been described in patients with normal renal function receiving magnesium sulfate in combination with multiple-dose activated charcoal.

1) Doses of 100 grams every 4 hours (total magnesium 90 grams) (Fassler et al, 1985) and 75 g/hr for 6 doses (total magnesium 44.6 grams) (Smilkstein et al, 1988).

d) Single doses of 30 grams of magnesium sulfate produced no significant elevation in magnesium serum levels in a study of 10 overdose patients.

1) In 14 patients who received 3 doses at 0, 4, and 8 hours after admission, serum magnesium levels were significantly elevated in 9 patients (2.2 to 5 mEq/L). All had normal baseline renal function (Smilkstein et al, 1988a).

2) ADULT

a) CASE REPORT: A 65-year-old man with a history of colon adenocarcinoma who was admitted for management of hypokalemia and hypomagnesemia secondary to diarrhea, developed lightheadedness, a heavy feeling in his arms, slurred speech, and a reduced Glasgow Coma Scale score of 12/15 after receiving IV infusions of potassium chloride and magnesium sulfate. No hemorrhage or evidence of acute ischemic injury was observed in a CT scan of the head. Laboratory results revealed an elevated magnesium concentration (3.55 mmol/L). At this time, it was determined that the magnesium infusion was inadvertently prepared using 50 mL (five 10 mL ampoules) of magnesium sulfate 50% (2 mmol/mL) instead of 6 mL of magnesium sulfate 50% (100 mmol [25 g of magnesium IV over about 2 hours instead of the prescribed 12 mmol [3 g]). He recovered gradually over the next 6 hours following supportive care. His magnesium concentrations 10 hours after the overdose and the following day were 1.57 mmol/L and 0.86 mmol/L, respectively (Cavell et al, 2015).
b) CASE REPORT: A woman developed asystole approximately 6 hours after ingesting 50 grams of Epsom salts (400 mEq magnesium). After resuscitation, prolonged QT and QRS complexes developed. She improved over 7 days with supportive therapy (Qureshi & Melonakos, 1996).
c) CASE REPORT: Symptomatic hypermagnesemia was reported following ingestion of 3 tablespoonfuls (750 mmol) of magnesium sulfate in an adult with normal renal function (Gerard et al, 1988).
d) CASE REPORT: A 36-year-old pregnant woman at 32 weeks gestation with a diagnosis of preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, underwent an emergent cesarean delivery under general anesthesia and delivered a live male infant with Apgar scores of 4 and 8 at 1 and 5 minutes, respectively. Because of suboptimal uterine tone noted about 10 minutes after delivery, the obstetrician requested an increase in the rate of the oxytocin infusion from 125 mL/hr to 240 mL/hr. However, the anesthetist inadvertently increased the magnesium infusion from 12.5 mL/hr to 240 mL/hr. After surgery was completed, there were no signs of arousal and tidal volume was only 30 mL. At this time, magnesium toxicity was considered and it was estimated that the patient had received about 13 g of magnesium over 40 minutes. An ECG showed markedly peaked T-waves. Following supportive care, including the administration of 10 mL of IV 10% calcium gluconate, her tidal volume increased to about 250 mL and she opened her eyes to command. Since she still had an erratic respiratory pattern and could not move her limbs or fingers, she was re-sedated and given another 10 mL bolus of 10% calcium gluconate, normal saline 1 L, furosemide 20 mg, and a dextrose-insulin infusion (human Actrapid 10 units in 50 mL of 50% glucose over 1 hours). Her condition improved within 30 minutes of the dextrose-insulin infusion as observed by her ECG and normalizing respiratory pattern. Her condition continued to improve over the next few days and she was discharged on day 5. Her infant underwent invasive ventilation, and was discharged after 34 days of hospitalization in good condition (McDonnell et al, 2010).

3) PEDIATRIC

a) CASE REPORT: Hypermagnesemia (14.9 mg/dL) was reported in a 14-year-old girl after receiving 18 g/day of a magnesium hydroxide-containing cathartic for 7 days. Following supportive therapy and hemodialysis, she made a full recovery and was discharged without recurrence of hypermagnesemia (Kutsal et al, 2007).
b) CASE REPORT: Hypermagnesemia with associated lethargy and apneic episodes occurred in a 6-week-old infant following administration of 16 doses of 1/3 of a teaspoon of magnesium hydroxide suspension containing 550 mg/10 mL during a 48 hour period (Alison & Bulugahapitiya, 1990).
c) CASE REPORT: A 25-day-old infant survived after receiving a total of 1297.4 mg elemental magnesium (381.6 mg/kg/day) (Mofenson & Caraccio, 1991).

C)

1) RECTAL

a) Acute magnesium toxicity, (magnesium 7.1 mmol/L) was reported in a 25-month-old female following administration and retention of a single magnesium sulfate enema containing 32.5 grams magnesium sulfate (Ashton et al, 1990).

2) INTRATHECAL

a) A 23-year-old woman, 22 weeks pregnant, suffered transient (6 hours) paralysis of her legs after receiving 2 mL of 50% magnesium sulfate intrathecally for insertion of a McDonald stitch for incompetent cervix. Six weeks later the patient miscarried, but it is not known if this was related to her incompetent cervix, the magnesium, or neither event (Lejuste, 1985).

3) EPIDURAL

a) A 26-year-old parturient patient inadvertently received up to 3 grams of magnesium sulfate via epidural infusion. She later delivered a normal infant via Cesarean section and seemed to suffer no long-term effects (Dror & Henriksen, 1987).
b) Two pregnant women in labor who inadvertently received magnesium sulfate in their epidural space, did not develop any evidence of neurological toxicity. One patient received 87 mL (8.7 g) of magnesium sulfate over approximately 1 hour and the second patient received 96 mL (9.6 g) of magnesium sulfate over 6.5 hours (Goodman et al, 2006).

4) INTRAVENOUS

a) A 23-year-old parturient patient received approximately 200 grams magnesium sulfate via intravenous infusion over 24 hours, then inadvertently received 20 grams over 15 minutes. The patient required intubation and intensive care, and survived despite a blood magnesium level of 38.7 mg/dL (Bohman & Cotton, 1990).
b) A pregnant woman with severe pre-eclampsia who required an emergency caesarean section received a loading dose of magnesium sulfate (4 g of 50% solution [8 mL]) followed by an entire syringe (25 g) of magnesium sulfate over approximately 40 minutes. ECG remained normal and she did not develop any symptoms of magnesium toxicity. Another pregnant woman with an eclamptic seizure received a loading dose of magnesium and approximately 13 g of magnesium sulfate. She did not develop any symptoms of magnesium toxicity (Buettner, 2011).

Serum Plasma Blood Concentrations

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) GENERAL

a) Serum magnesium concentrations and associated signs/symptoms are reported as follows (Jones et al, 1986):

1) Nausea and vomiting may be seen at serum magnesium levels of 3 mEq/L.
2) Drowsiness, sweating, and unsteadiness at 4 mEq/L.
3) QRS widening and PR prolongation at 5 mEq/L.
4) Bradycardia and hypotension at 6 to 7 mEq/L.
5) Voluntary muscle paralysis, heart block, and respiratory paralysis at 10 to 15 mEq/L.

CONCENTRATION LEVEL

b) Signs of hypermagnesemia may occur at plasma concentrations in excess of 4 mEq/L (2 mmol/L) (JEF Reynolds , 1991).

CASE REPORTS

c) ADULT - A patient survived an iatrogenic hypermagnesemia of 38.7 mg/dL (Bohman & Cotton, 1990) and another survived following a serum magnesium level of 21.7 mg/dL (Qureshi & Melonakos, 1996).

d) ADULT - Following the ingestion of 4 tablespoonfuls of Epsom salts (magnesium sulfate 140 mEq/17.5 grams), a 47-year-old female developed altered mental status and diffuse motor weakness, with a serum magnesium concentration of 18.3 mEq/L. She recovered following fluid resuscitation (Nordt et al, 1996).

e) ADULT - A woman with normal renal function developed severe hypermagnesemia (magnesium level 9.8 mmol/L (23.6 mg/dL)) following chronic gargling with Epsom salt for halitosis. She experienced coma, hypotension, acute renal failure, and multiple episodes of asystole and ventricular fibrillation requiring repeated defibrillation. Despite intensive care, including hemodialysis, she died of a cardiac arrest (Birrer et al, 2002).

f) PEDIATRIC - A 16-year-old girl who received a bone marrow transplant 45 days before presentation, developed hypermagnesemia (magnesium level 5.9 mmol/L) resulting in hypotension, hypothermia, and coma after ingesting 15 mL of magnesium-containing antacid every 2 hours instead of 4 times daily. Following supportive care, she recovered completely (Jaing et al, 2002).

g) PEDIATRIC - Hypermagnesemia (14.9 mg/dL) was reported in a 14-year-old girl after receiving 18 g/day of magnesium hydroxide-containing cathartic for 7 days. Following supportive therapy and hemodialysis, she made a full recovery and was discharged without recurrence of hypermagnesemia (Kutsal et al, 2007).

h) INFANT - Two premature infants developed severe hypermagnesemia following inadvertent excessive exposure via total parenteral nutrition. Serum levels peaked at 43.1 mEq/L and 45 mEq/L, respectively. Only mild residual gross motor developmental delay was reported in one infant (Ali et al, 2003).

i) PEDIATRIC - Fatal hypermagnesemia (serum magnesium 3.2 mmol/L; normal <1.2 mmol/L) was reported in a 2.5-year-old boy after his mother gave him magnesium oxide supplements as needed to regulate bowel function (Kulkarni et al, 1999).

Pharmacology Toxicology

Pharmacologic Mechanism

A)

1) Electrophysiologic effects include prolongation of the PR interval, AH interval, AV nodal effective refractory period, and sinoatrial conduction time. Calcium channel blockade has also been demonstrated (Kulick et al, 1988).

Toxicologic Mechanism

A)

B)

1) Magnesium deficiency is thus not uncommon in association with digitalis toxicity and administration of parenteral magnesium may be essential to control of arrhythmias.

C)

D)

Physicochemical

Physical Characteristics

A)

Molecular Weight

A)

Other

A)

1) Odorless (CHRIS , 2002)

Animal Toxicology

Clinical Effects

11.1.2)

A) Side effects of high doses of orally administered magnesium hydroxide in cattle include hypermagnesemia, metabolic alkalosis, diarrhea, and possible coma and death.

1) Abnormal electrolyte levels in the affected animals include increased Mg, HCO3, and base excess (Kasari, et al, 1990).

B) Cattle not getting enough magnesium in the diet may suffer from hypomagnesemic tetany. This is most commonly seen in cows grazing lush pastures during early lactation (Chester-Jones et al, 1989).

11.1.5)

A) Adverse effects of toxic oral doses of magnesium sulfate administered to horses have resulted in agitation, sweating, generalized tremors, tachycardia, and tachypnea. Severe cases have resulted in flaccid paralysis of neck and limb muscles, with absent flexor and perineal reflexes (Henninger & Horst, 1997).

11.1.9)

A) Sheep being test-fed high levels of magnesium showed signs of diarrhea (Chester-Jones et al, 1989).

Treatment

11.2.1)

A) GENERAL TREATMENT

1) SUMMARY

a) Begin treatment immediately.
b) Keep animal warm and do not handle unnecessarily.
c) Remove the patient and other animals from the source of contamination or remove dietary sources.

2) Treatment should always be done on the advice and with the consultation of a veterinarian.
3) Additional information regarding treatment of poisoned animals may be obtained from a Veterinary Toxicologist or the National Animal Poison Control Center.
4) ASPCA ANIMAL POISON CONTROL CENTER

a) ASPCA Animal Poison Control Center, 1717 S Philo Road, Suite 36 Urbana, IL 61802
b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
c) Contact information: (888) 426-4435 (hotline) or www.aspca.org (A fee may apply. Please inquire with the poison center). The agency will make follow-up calls as needed in critical cases at no extra charge.

5) LARGE ANIMALS: Due to lack of reports of small animal intoxication with this substance, the following sections address large animals (horses and ruminants) only.
6) In the case of a poisoning involving small animals, consult a veterinary poison control center.

11.2.2)

A) GENERAL

1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.

11.2.4)

A) GASTRIC DECONTAMINATION

1) GENERAL TREATMENT

a) EMESIS/GASTRIC LAVAGE -

1) CAUTION: Carefully examine patients with chemical exposure before inducing emesis. If signs of oral, pharyngeal, or esophageal irritation, a depressed gag reflex, or central nervous system excitation or depression are present, EMESIS SHOULD NOT BE INDUCED.
2) HORSES OR CATTLE: DO NOT attempt to induce emesis in ruminants (cattle) or equids (horses).
3) DOGS AND CATS

a) IPECAC: If within 2 hours of exposure: induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os.
b) APOMORPHINE: Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os.

1) Dogs may also be given apomorphine intravenously at 40 micrograms/kilogram, although this route may not be as effective.

4) LAVAGE: In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage.

a) Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times.

5) RUMEN LAVAGE - In conscious animal, insert stomach tube through mouth gag and use gently flowing tap water to wash out the rumen. Instill activated charcoal and leave it in the rumen.

b) ACTIVATED CHARCOAL -

1) HORSES - Administer 0.5 to 1 kilogram of activated charcoal in up to 1 gallon warm water via nasogastric tube. Neonates: administer 250 grams in up to 2 quarts water.
2) RUMINANTS - Administer 2 to 9 grams/kilogram activated charcoal in a water slurry. Sheep may be given 0.5 kilogram charcoal in slurry.
3) Cathartics are NOT recommended.

11.2.5)

A) GENERAL TREATMENT

1) MAINTAIN VITAL FUNCTIONS - as necessary.
2) FLUID THERAPY -

a) HORSE: Administer electrolyte and fluid therapy as needed. Maintenance dose of intravenous isotonic fluids: 10 to 20 milliliters/ kilogram per day. High dose for shock: 20 to 45 milliliters/kilogram/hour.

1) Monitor for packed cell volume, adequate urine output and pulmonary edema. Goal is to maintain a urinary flow of 0.1 milliliters/kilogram/minute (2.4 liters/hour for an 880 pound horse).

b) CATTLE: Administer electrolyte and fluid therapy, orally or parenterally as needed. Maintenance dose of intravenous isotonic fluids for calves and debilitated adult cattle: 140 milliliters/kilogram/day. Dose for rehydration: 50 to 100 milliliters/kilogram given over 4 to 6 hours.

3) CALCIUM GLUCONATE -

a) HORSES - Following severe magnesium toxicosis in horses, a 23% solution of calcium gluconate (diluted in 1 liter of 0.9% sodium chloride solution) has been administered slowly, intravenously, with a return to normal of heart and respiratory rate and improved neuromuscular function. This dose may be repeated as needed (Henninger & Horst, 1997). To promote diuresis, rapid administration of lactated Ringer's solution (up to 10 liters) should also be given as an intravenous infusion.

Range Of Toxicity

11.3.1)

A) CATTLE

1) Approximately 20 grams magnesium/day given to a lactating cow will maintain serum Mg levels at 2 milligrams/deciliter (Chester-Jones et al, 1989).

B) HORSES

1) Recommended dosage as a laxative for treatment of equine impactions ranges from 0.5 to 1.0 gram/kilogram (0.25 to 0.45 gram/pound) diluted in 4 to 6 liters of water (Henninger & Horst, 1997).

11.3.2)

A) HORSES

1) A dose of approximately 0.75 kilograms (1.5 pounds) of magnesium sulfate administered via a nasogastric tube to a 450 kg (990 pounds) horse resulted in severe neuromuscular toxicity with tachycardia and tachypnea (Henninger & Horst, 1997).

Continuing Care

11.4.1)

11.4.1.2) DECONTAMINATION/TREATMENT

A) GENERAL TREATMENT

1) SUMMARY

a) Begin treatment immediately.
b) Keep animal warm and do not handle unnecessarily.
c) Remove the patient and other animals from the source of contamination or remove dietary sources.

2) Treatment should always be done on the advice and with the consultation of a veterinarian.
3) Additional information regarding treatment of poisoned animals may be obtained from a Veterinary Toxicologist or the National Animal Poison Control Center.
4) ASPCA ANIMAL POISON CONTROL CENTER

a) ASPCA Animal Poison Control Center, 1717 S Philo Road, Suite 36 Urbana, IL 61802
b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
c) Contact information: (888) 426-4435 (hotline) or www.aspca.org (A fee may apply. Please inquire with the poison center). The agency will make follow-up calls as needed in critical cases at no extra charge.

5) LARGE ANIMALS: Due to lack of reports of small animal intoxication with this substance, the following sections address large animals (horses and ruminants) only.
6) In the case of a poisoning involving small animals, consult a veterinary poison control center.

11.4.2)

11.4.2.2) GASTRIC DECONTAMINATION

A) GASTRIC DECONTAMINATION

1) GENERAL TREATMENT

a) EMESIS/GASTRIC LAVAGE -

1) CAUTION: Carefully examine patients with chemical exposure before inducing emesis. If signs of oral, pharyngeal, or esophageal irritation, a depressed gag reflex, or central nervous system excitation or depression are present, EMESIS SHOULD NOT BE INDUCED.
2) HORSES OR CATTLE: DO NOT attempt to induce emesis in ruminants (cattle) or equids (horses).
3) DOGS AND CATS

a) IPECAC: If within 2 hours of exposure: induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os.
b) APOMORPHINE: Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os.

1) Dogs may also be given apomorphine intravenously at 40 micrograms/kilogram, although this route may not be as effective.

4) LAVAGE: In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage.

a) Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times.

5) RUMEN LAVAGE - In conscious animal, insert stomach tube through mouth gag and use gently flowing tap water to wash out the rumen. Instill activated charcoal and leave it in the rumen.

b) ACTIVATED CHARCOAL -

1) HORSES - Administer 0.5 to 1 kilogram of activated charcoal in up to 1 gallon warm water via nasogastric tube. Neonates: administer 250 grams in up to 2 quarts water.
2) RUMINANTS - Administer 2 to 9 grams/kilogram activated charcoal in a water slurry. Sheep may be given 0.5 kilogram charcoal in slurry.
3) Cathartics are NOT recommended.

Kinetics

11.5.1)

A) HORSES

1) Magnesium sulfate is absorbed almost exclusively from the small intestine, with absorption beginning within one hour after ingestion and continuing for up to 8 hours. Percentage of magnesium absorbed has an inverse relationship with the oral magnesium dose and serum magnesium concentration. Normal absorption ranges from 40% to 70% (Henninger & Horst, 1997).

References

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MAGNESIUM

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Genitourinary

Dermatologic

Musculoskeletal

Reproductive

Carcinogenicity

Monitoring Parameters Levels

Methods

Life Support

Patient Disposition

Monitoring

Oral Exposure

Enhanced Elimination

Case Reports

Workplace Standards

Toxicity Information

Summary

Therapeutic Dose

Minimum Lethal Exposure

Maximum Tolerated Exposure

Serum Plasma Blood Concentrations

Pharmacologic Mechanism

Toxicologic Mechanism

Physical Characteristics

Molecular Weight

Other

Clinical Effects

Treatment

Range Of Toxicity

Continuing Care

Kinetics

General Bibliography