Effect of Magnesium Sulfate Infusion Rate on Magnesium Retention in Critically Ill Patients
| Status: | Completed |
|---|---|
| Conditions: | Hospital |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 3/1/2014 |
| Start Date: | April 2011 |
| End Date: | December 2012 |
| Contact: | Jack L DePriest, MD |
| Email: | jdepriest@hsc.wvu.edu |
| Phone: | 304-347-1286 |
Hypomagnesemia (low magnesium) is an electrolyte imbalance commonly found in up to 65% of
critically ill patients. Possible consequences of hypomagnesemia include neuromuscular and
neurologic dysfunction, heart arrhythmias, and alterations in other electrolytes. Data has
shown that critically ill patients with hypomagnesemia have a significantly higher mortality
rate than patients with a normal magnesium level. The most simple and commonly used test to
diagnose hypomagnesemia is a serum magnesium level. Based on the magnesium level and
symptoms of hypomagnesemia, patients may be replaced with either oral or intravenous (IV)
magnesium. When replacing magnesium via the IV route, approximately half of the dose is
retained by the body while the remainder is excreted in the urine. The low retention rate is
due to the slow uptake of magnesium by cells and decreased magnesium reabsorption by the
kidneys in response to the delivery of a large concentration of magnesium. The purpose of
this study is to determine whether an eight hour compared to a four hour infusion of IV
magnesium sulfate results in a greater retention of the magnesium dose.
critically ill patients. Possible consequences of hypomagnesemia include neuromuscular and
neurologic dysfunction, heart arrhythmias, and alterations in other electrolytes. Data has
shown that critically ill patients with hypomagnesemia have a significantly higher mortality
rate than patients with a normal magnesium level. The most simple and commonly used test to
diagnose hypomagnesemia is a serum magnesium level. Based on the magnesium level and
symptoms of hypomagnesemia, patients may be replaced with either oral or intravenous (IV)
magnesium. When replacing magnesium via the IV route, approximately half of the dose is
retained by the body while the remainder is excreted in the urine. The low retention rate is
due to the slow uptake of magnesium by cells and decreased magnesium reabsorption by the
kidneys in response to the delivery of a large concentration of magnesium. The purpose of
this study is to determine whether an eight hour compared to a four hour infusion of IV
magnesium sulfate results in a greater retention of the magnesium dose.
Hypomagnesemia is a common electrolyte disturbance that affects up to 65% of intensive care
unit (ICU) patients with normal renal function. Causes of hypomagnesemia are attributed to
either gastrointestinal (secretory loss, impaired absorption or reabsorption, acute
pancreatitis) or renal losses (alcohol, hypercalcemia, volume expansion, loop or thiazide
diuretics, nephrotoxic medications, renal tubular dysfunction, inborn disorders).
Consequences of magnesium deficiency are not benign and may include neuromuscular and
neurologic dysfunction, cardiac arrhythmias and concomitant electrolyte abnormalities
including hypokalemia and hypocalcemia. Hypomagnesemia has been associated with a
significantly greater mortality rate in critically ill medical patients compared to
normomagnesemic patients. In a study conducted by Rubeiz et al, 46% (17/37) of
hypomagnesemic patients in the medical ICU died compared to 25% (37/147) of normomagnesemic
patients (p < 0.05).
It can be difficult to assess patients for hypomagnesemia because of the unreliable
relationship between serum and tissue magnesium levels. Approximately 1% of total body
magnesium is found in the extracellular fluid while the remaining 99% is distributed among
the bones, muscles, and soft tissues. Approximately 60% of serum magnesium is free ions; 33%
is bound to proteins and 7% is complexed with anions. The most simple and commonly used test
to diagnose hypomagnesemia is the total serum magnesium level which reflects free magnesium
along with complexed and protein bound magnesium. The serum magnesium level, however, is
not always accurate at detecting magnesium deficiency. Patients may appear to be
normomagnesemic based on their serum magnesium level, yet have an underlying magnesium
deficiency. Normal serum magnesium levels vary by laboratory. The normal range of values at
Charleston Area Medical Center (CAMC) is 1.6-2.6 mg/dL.
Magnesium replacement depends on the clinical situation and manifestations. In critical
conditions such as pre-eclampsia, arrhythmias, and tetany, large doses of IV magnesium are
rapidly bolused and often followed by a continuous IV infusion. In asymptomatic patients,
magnesium may be replaced by the oral or IV route depending on the clinical situation. The
dose required to return patients to the normal magnesium range is variable and replacement
may take several doses. Serum magnesium levels are primarily controlled by glomerular
filtration and tubular reabsorption at the sites of the Loop of Henle and distal tubule.
When faced with an increased filtered load of magnesium, the kidney is capable of increasing
its excretion rate. Following intravenous (IV) administration, cellular magnesium uptake is
slow and approximately 50% or more of the infused dose is lost due to increased excretion by
the kidneys and decreased tubular reabsorption.
The investigators current practice in the Medical and Neuroscience ICUs at CAMC General
Hospital is to order 8g of magnesium sulfate for replacement in patients with
hypomagnesemia. When IV magnesium sulfate is ordered the pharmacy automatically sets the
rate to run at 2g per hour unless otherwise specified. Often times the physician will
specify for 8g to be infused over eight hours. The basis of using an extended infusion is
that a slower magnesium infusion rate may increase magnesium retention by allowing a longer
period of time for magnesium uptake by cells and by decreasing the magnesium load delivered
to the kidneys at any given time. As far as the investigators are aware, there have been no
studies completed to date that assess the rate of IV magnesium infusion on the magnesium
retention rate.
unit (ICU) patients with normal renal function. Causes of hypomagnesemia are attributed to
either gastrointestinal (secretory loss, impaired absorption or reabsorption, acute
pancreatitis) or renal losses (alcohol, hypercalcemia, volume expansion, loop or thiazide
diuretics, nephrotoxic medications, renal tubular dysfunction, inborn disorders).
Consequences of magnesium deficiency are not benign and may include neuromuscular and
neurologic dysfunction, cardiac arrhythmias and concomitant electrolyte abnormalities
including hypokalemia and hypocalcemia. Hypomagnesemia has been associated with a
significantly greater mortality rate in critically ill medical patients compared to
normomagnesemic patients. In a study conducted by Rubeiz et al, 46% (17/37) of
hypomagnesemic patients in the medical ICU died compared to 25% (37/147) of normomagnesemic
patients (p < 0.05).
It can be difficult to assess patients for hypomagnesemia because of the unreliable
relationship between serum and tissue magnesium levels. Approximately 1% of total body
magnesium is found in the extracellular fluid while the remaining 99% is distributed among
the bones, muscles, and soft tissues. Approximately 60% of serum magnesium is free ions; 33%
is bound to proteins and 7% is complexed with anions. The most simple and commonly used test
to diagnose hypomagnesemia is the total serum magnesium level which reflects free magnesium
along with complexed and protein bound magnesium. The serum magnesium level, however, is
not always accurate at detecting magnesium deficiency. Patients may appear to be
normomagnesemic based on their serum magnesium level, yet have an underlying magnesium
deficiency. Normal serum magnesium levels vary by laboratory. The normal range of values at
Charleston Area Medical Center (CAMC) is 1.6-2.6 mg/dL.
Magnesium replacement depends on the clinical situation and manifestations. In critical
conditions such as pre-eclampsia, arrhythmias, and tetany, large doses of IV magnesium are
rapidly bolused and often followed by a continuous IV infusion. In asymptomatic patients,
magnesium may be replaced by the oral or IV route depending on the clinical situation. The
dose required to return patients to the normal magnesium range is variable and replacement
may take several doses. Serum magnesium levels are primarily controlled by glomerular
filtration and tubular reabsorption at the sites of the Loop of Henle and distal tubule.
When faced with an increased filtered load of magnesium, the kidney is capable of increasing
its excretion rate. Following intravenous (IV) administration, cellular magnesium uptake is
slow and approximately 50% or more of the infused dose is lost due to increased excretion by
the kidneys and decreased tubular reabsorption.
The investigators current practice in the Medical and Neuroscience ICUs at CAMC General
Hospital is to order 8g of magnesium sulfate for replacement in patients with
hypomagnesemia. When IV magnesium sulfate is ordered the pharmacy automatically sets the
rate to run at 2g per hour unless otherwise specified. Often times the physician will
specify for 8g to be infused over eight hours. The basis of using an extended infusion is
that a slower magnesium infusion rate may increase magnesium retention by allowing a longer
period of time for magnesium uptake by cells and by decreasing the magnesium load delivered
to the kidneys at any given time. As far as the investigators are aware, there have been no
studies completed to date that assess the rate of IV magnesium infusion on the magnesium
retention rate.
Inclusion Criteria:
Medicine ICU service patients
- > 18 years old with
- hypomagnesemia defined by a serum magnesium level < 2 mg/dL and the clinical decision
by the rounding team to replace with parenteral magnesium sulfate
- must have an available IV line for magnesium infusion that may be used for up to 8
hours
- must have a Foley catheter
Exclusion Criteria:
- renal dysfunction defined by an estimated creatinine clearance (CrCl) < 30 mL/min or
have had an average of < 0.5 mL/kg/hr of urine output over the previous 12 hours
before the magnesium infusion is to begin
- Subjects must not have received a loop diuretic within the 12 hours prior to
magnesium replacement and will further be excluded if they receive these medications
during the magnesium replacement and urine collection time period
- Subjects with ostomies or acute diarrhea will be excluded due to the possibility of
high gastrointestinal magnesium loss
- Subjects will be excluded if they have a physician order for magnesium sulfate to be
infused over a specified time period
- If subjects are expected to be moved out of the ICU within the next 24 hours, they
will not be considered for randomization due to potential lack of appropriate urine
magnesium collection and follow up
- Each subject may only be enrolled in the study for one occurrence of hypomagnesemia
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