Effect of Magnesium Sulfate Infusion Rate on Magnesium Retention in Critically Ill Patients

This study has been terminated.
(Issues with recruitment. PI decided to terminate study)
Sponsor:
Collaborator:
Sara and Pauline Maier Foundation, Inc.
Information provided by (Responsible Party):
Carol Morreale, CAMC Health System
ClinicalTrials.gov Identifier:
NCT01426165
First received: August 24, 2011
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention
Primary Hypomagnesemia (Disorder)
Drug: Magnesium Sulfate

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Magnesium Sulfate Infusion Rate on Magnesium Retention in Critically Ill Patients

Resource links provided by NLM:


Further study details as provided by CAMC Health System:

Primary Outcome Measures:
  • Amount of urinary excretion of magnesium after an 8g magnesium sulfate infusion delivered over 4 hours versus 8 hours. [ Time Frame: 24 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean change in the serum magnesium level after an 8 gm magnesium sulfate infusion delivered over 4 hours and 8 hours [ Time Frame: 24 hours ] [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: April 2011
Study Completion Date: December 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Magnesium 8 grams over 4 hours Drug: Magnesium Sulfate
8 grams over 4 or 8 hours depending on randomization
Other Name: magnesium
Experimental: Magnesium 8 grams over 8 hours Drug: Magnesium Sulfate
8 grams over 4 or 8 hours depending on randomization
Other Name: magnesium

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01426165

Locations
United States, West Virginia
Charleston Area Medical Center
Charleston, West Virginia, United States, 25301
Sponsors and Collaborators
CAMC Health System
Sara and Pauline Maier Foundation, Inc.
Investigators
Principal Investigator: Jack L DePriest, MD WVU School of Medicine/Charleston Division
  More Information

Publications:
Responsible Party: Carol Morreale, Clinical Pharmacist Specialist - Emergency Medicine/Critical Care; Director, PGY2 Pharmacy Residency in Critical Care, CAMC Health System
ClinicalTrials.gov Identifier: NCT01426165     History of Changes
Other Study ID Numbers: 10-10-2271
Study First Received: August 24, 2011
Last Updated: January 31, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by CAMC Health System:
hypomagnesemia
magnesium
magnesium sulfate

Additional relevant MeSH terms:
Critical Illness
Nephrocalcinosis
Renal Tubular Transport, Inborn Errors
Hypercalciuria
Disease Attributes
Pathologic Processes
Kidney Diseases
Urologic Diseases
Calcinosis
Calcium Metabolism Disorders
Metabolic Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Urological Manifestations
Signs and Symptoms
Magnesium Sulfate
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics
Central Nervous System Depressants
Anti-Arrhythmia Agents
Cardiovascular Agents
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators

ClinicalTrials.gov processed this record on July 20, 2014