DO IONIZED MAGNESIUM LEVELS PREDICT CLINICAL EFFECTS BETTER THAN TOTAL MAGNESIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Intravenous magnesium sulfate (MgS04) is widely used in obstetrics for the treatment of both preterm labor (PTL) and pregnancy induced hypertension (PI H). However, there is little information regarding optimal dosage and therapeutic levels, as it is not possible to correlate Mg levels with changes in uterine contractions or blood pressure. the form of magnesium commonly measured is total magnesium (tMg). We recently demonstrated that levels of the active form of magnesium, free or ionized (iMg) do not correlate well with tMglevels. The purpose of this study is to determine whether iMg concentrations correlate better than tMg with changes in nerve conduction. Women of child bearing potential, over the age of 18, seen at this center, are eligible for participation in this study. 10 pregnant patients requiring Mg for preterm labor and 10 pregnant patients requiring Mg for pregnancy hypertension will be studied. An indwelling intravenous catheter will be placed for all blood draws. Blood will be drawn for serum creatinine levels before initiation of Mg treatment. Subjects will be excluded for creatinine levels greater than 1.2mg/dL (Harbor¿UCLA upper limit of normal). Patients with renal disease, history of hypersensitivity to magnesium, and history of a medical condition which would be impacted by the magnesium (such as myasthenia gravis) or history of a cardio¿pulmonary condition, will also be excluded from the study. Each subject will have a baseline blood level to determine basal magnesium (tMg and iMg) levels. Magnesium levels will.1 also be determined hourly for the duration of the study. Serum calcium levels will be determined along with magnesium. At hourly intervals throughout the infusion and post infusion periods, magnesium levels (total and ionized) will be obtained, and ulnar nerve conduction studies (NCS) will be performed. The NCS will consist of a total of ten electrical shocks. These will be repeated at three hOurly intervals for a total of 30 shocks. These shocks are mildly uncomfortable to most people. During Mg infusion, all subjects will have respiratory rate, blood pressure and uterine activity logged every hour. Deep tendon reflexes (DTR) will also be tested at each blood determination to assess magnesium effects. Magnesium infusions will be discontinued if oxygen saturation falls below 92% or by 5%, if cardiac arrhythmias occur, for development of somnolence, or from the loss of DTRs. All patients will be closely monitored as well as clinically treated and observed by nursing staff and physicians on duty. The magnesium infusion will run thru a separate IV access site. All pregnant patients in this study will be receiving required therapeutic magnesium sulfate for preterm labor or pregnancy hypertension. All Mg infusions will be administered as an initial bolus of 4-6 grams, given over twenty to thirty minutes. This will be followed by an infusion of 2-3 gm/hr for a total of four hours. After the four hours the magnesium sulfate will be continued as clinically indicated. Risks to patients appear to be minimal for long-term effects. Most individuals will experience some discomfort ranging from mild to severe. There is no benefit to individuals participating in this study. All patients participating in this study will be receiving Mg-sulfate as clinically indicated for preterm labor or preeclampsia per standard clinical criteria despite whether or not they continue with the study. Magnesium will be administered per standard protocol for preterm labor and preclampsia. In this study Mg is the research intervention being studied but it is also the standard clinical intervention for these conditions. The clinical criteria for diagnosis preterm labor are uterine contractions and cervical change. The clinical criteria for preeclampsia are blood pressure> 140/90 and proteinuria (24 hour urine collection greater than 300 mg or 1 + protein on urine dipstick). Mg is the treatment and it is administered in the same manner whether or not the patient is in the study or does not participate in the study. There may be benefits to future patients, if the results of the study allow safer use of magnesium in clinical practice. This would clinically improve monitoring of the therapeutic levels in patients and decrease toxic levels of magnesium sulfate.