Volume 163 Number 3
maturational process that occurs in the baseline FHR and FHR acceleration with advancing gestational age, the difference in mean gestational age of 1.9 weeks seen between the gram-positive and gram-negative groups is not great enough to account for the statistically significant difference in FHR reactivity and baseline heart rate observed between the two groupS." Because amniocentesis is invasive and difficult to perform in patients with PROM (especially those with very low fluid volume), many clinicians do not include amniotic fluid Gram stain and culture in the routine assessment of patients with preterm PROM. The diagnosis of early or subclinical chorioamnionitis, although desirable, is difficult in the absence of fever. Symptoms such as leukocytosis are quite nonspecific. The data presented here would support that the presence of fetal tachycardia (FHR > 150 beats/min) and nonreactive FHR tracing is highly suggestive of occult intraamniotic infection, and that amniocentesis to verify this suspicion is warranted. We thank Lanie M. Adamson, MS, Linda Salyer, and Elaine Baker for their assistance. REFERENCES I. Gibbs RS, Blanco jD. Premature rupture of the membranes. Obstet Gynecol 1982;60:671-9.
Gram stain results of amniocentesis
2. Garite Tj, Freeman RK, Linzy EM, Braly P. The use of amniocentesis in patients with premature rupture of membranes. Obstet Gynecol 1979;54:226-30. 3. Garite Tj. Premature rupture of membranes: the enigma of the obstetrician. AM j OBSTET GYNECOL 1985;151: 1001-5. 4. Vintzileos AM, Campbell WA, Nochimson Dj, Weinbaum Pj. Fetal breathing as a predictor of infection in premature rupture of membranes. Obstet Gynecol 1986;67: 813-7. 5. Goldstein I, Romero R, Merrill S, et al. Fetal body and breathing movements as predictors of intraamniotic infection in preterm premature rupture of membranes. AM j OBSTET GYNECOL 1988; 159:363-8. 6. Vintzileos AM, Campbell WA, Nochimson Dj, et al. The fetal biophysical profile in patients with premature rupture of membranes-an early predictor of fetal infection. AMj OBSTET GYNECOL 1985;152:510-6. 7. Vintzileos AM, Feinstein Sj, Lodeiro jG, et al. Fetal biophysical profile and the effect of premature rupture of the membranes. Obstet Gynecol 1986;67:818-23. 8. Cotton DB, Hill LM, Strassner HT, et al. Use of amniocentesis in preterm gestation with ruptured membranes. Obstet Gynecol 1984;63:38-43. 9. Gonik B, Cotton DB. The use of amniocentesis in preterm premature rupture of membranes. Am j Perinatol 1985; 2:221-4. 10. Moberg Lj, Garite Tj, Freeman RK. Fetal heart rate patterns and fetal distress in patients with preterm premature rupture of membranes. Obstet Gynecol 1984;64:60. II. Gagnon R, Campbell K, Hunse C, Patrick J. Patterns of human fetal heart rate acclerations from 26 weeks to term. AM j OBSTET GYNECOL 1987;157:743-8.
Adjusting the loading dose of magnesium sulfate for tocolysis Jeffrey W. Wright, MD, Louis E. Ridgway III, MD, and Robert M. Patterson, MD San Antonio, Texas The purpose of this prospective study was to establish a method to calculate a loading dose of magnesium sulfate so as to achieve therapeutic levels of tocolysis more quickly. Fifty patients in preterm labor were enrolled. In the first phase 25 patients were studied so that the apparent volume of distribution for the loading dose of magnesium sulfate could be estimated and an adjusted loading dose could be calculated. The efficacy of this adjusted loading dose was then tested on a further 25 patients in the second phase. We found that the apparent volume of distribution could be accurately estimated and an adjusted loading dose calculated, with the use of ideal body weight, degree of underweight, and current use of ~-sympathomimetics. In the adjusted loading dose group therapeutic levels were achieved more often, with higher postloading magnesium levels and a greater decrease in contraction index immediately after the loading dose. We conclude that an adjusted loading dose can be calculated for magnesium sulfate to optimize tocolytic therapy. (AM J OBSTET GYNECOL 1990;163:889-92.)
Key words: Magnesium, magnesium dosage, tocolytics, magnesium pharmacology
From the Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio. Presented at the Tenth Annual Meeting of the Society of Perinatal Obstetricians, Houston, Texas, January 23-27, 1990. Reprint requests: jeffrey W. Wright, MD, Department of Obstetrics and Gynecology, UTHSCSA, 7703 Floyd Curl Dr., San Antonio,
TX 78284-7836. 616122354
Magnesium sulfate is a commonly used parenteral tocolytic. It has been shown to be as effective as 13sympathomimetics with a lower incidence of serious side effects. I·' However, a longer period of time is required to achieve uterine quiescence with magnesium than with j3-sympathomimetics. 1 Several studies have demonstrated a need to achieve
889
890 Wright, Ridgway, and Patterson
September 1990 Am J Obstet Gynecol
Table I. Ideal weight table Ideal weightt (kg) Height*
Small frame
Medium frame
Large frame
4'11" 5'0" 5'1" 5'2" 5'3" 5'4" 5'5" 5'6" 5'7" 5'8"
49.8 50.9 52 53.4 54.8 56.1 57.5 58.9 60.2 61.6
54.3 55.5 56.8 58.2 59.5 60.9 62.3 63.6 65 66.4
58.9 60.2 61.6 63.2 64.8 66.4 68.0 69.5 70.7 72.5
Modified from 1983 Metropolitan life table. *Height without shoes. tWeight in patient gown.
a minimum therapeutic concentration of magnesium ions to suppress uterine activity. I. '-6 However, these levels are rarely achieved with the typical 4 grn loading dose of magnesium sulfate. 5 To achieve a therapeutic level of magnesium while avoiding potential toxicity, knowledge of the volume of distribution of magnesium is needed. However, no previous studies address the issue of the volume of distribution for the loading dose of magnesium sulfate in patients in preterm labor. The goal of this study was to establish the apparent volume of distribution of the loading dose of magnesium sulfate so that an adjusted loading dose could be calculated and to in vestigate the efficacy of this adjusted loading dose. Material and methods
In this prospective study, 50 patients admitted to the labor and delivery unit with preterm labor were enrolled. Preterm labor was defined as a gestational age of 24 to 35 weeks and regular uterine contractions accompanied by documented cervical change. Choice of tocolytic agent was by individual physician preference. In general, magnesium is used in our institution as the first-line drug for tocolysis. Patients with preexistent renal disease, suspected dehydration, or a contraindication to tocolysis were excluded. The study was done in two phases with 25 patients in each phase. In phase I patients were given a 4 gm loading dose of magnesium sulfate (MgSO,' 7H 20 United States Pharmacopeia) infused intravenously over 15 minutes with an infusion pump. Blood samples for serum magnesium determination were drawn immediately before and 1 minute after the loading dose was given. Magnesium levels were determined by means of the calmagite reaction and a Paramax System (Baxter Scientific, Irvine, Calif.). Apparent volume of distribution (AVOD) was calculated by the equa-
tion: AVOD = MgSO, loading dose [grams] X 98 [milligrams Mg+ + per gram MgSO, 1 (Postloading level - preloading level [milligrams per deciliter]) x 100 mIl dl. This formula reduced to: AVOD = 39,2001 (Postloading level-Pre loading level). Because patients in pre term labor often receive significant volumes of intravenous fluids before tocolysis AVOn was corrected by the following equation: True AVOD = Measured AVOD - (Intravenous fluidsUrine output). For each patient, height, weight, ideal body weight, degree of weight over or under the ideal, gestational age, body surface area, presence of multiple gestation, previous exposure to magnesium, and current therapy with [3-sympathomimetic tocolytics were recorded. Ideal body weight was estimated by a modified 1983 Metropolitan life table. This table was generated by taking the midpoint of the range of ideal weight for a given height and frame size, converting it to kilograms, and correcting for lack of shoes and clothing (Table I). For overweight patients, overweight was calculated by: Overweight = Actual weight - Ideal weight. For underweight patients underweight was calculated by: Underweight = Ideal weight - Actual weight. Contraction monitor strips for 30 minutes before the loading dose began and 30 minutes after completion were photocopied for future analysis. After completion of the study, two blinded examiners scored the monitor strips for contraction index and number of contractions in 30 minutes. The contraction index was calculated as the total duration of contractions during 30 minutes of monitoring. Stepwise linear regression was used to establish the relationship between apparent volume of distribution and the independent variables weight, ideal weight, underweight, overweight, body surface area, multiple gestation, previous exposure to magnesium, and current therapy with [3-sympathomimetics. In phase 2, apparent volume of distribution was estimated by the equation established in phase 1: AVOn = 613.1 + 215.7 (Ideal weight in kilograms) + 408.3 (Underweight in kilograms) - 2182.7 (ifreceiving [3-sympathomimetic). The adjusted loading dose was calculated by this equation: Loading dose = AVOD [milliliters] X 5.2 [Expected change in serum Mg+ +] 1 (98 [milligrams Mg+ + per gram MgSO,] X 100 [milligrams per deciliter]). The simplified equations are shown in Table II. We assumed an approximate baseline level of 1.8 mg/dl and target level of 7 mg/dl. The minimum therapeutic level was.defined as 6 mg/dl. Magnesium infusion technique, as well as other treatment and data collection, was identical to that of phase 1. After phase 2 was completed, stepwise linear regression was again performed with study phase added as
Adjusting loading dose of magnesium
Volume 163 Number 3
Table II. Calculation of the adjusted loading dose Apparent volume of distribution = 613.1 + 215.7 (Ideal weight, kilograms) + 408.3 (Underweight, kilograms) - 2182.7 [If receiving 13sympathomimetic] Adjusted loading dose [grams] = 0.00053 x Apparent volume of distribution
*Appropriate safety precautions should be observed during
magnesium infusion.
an independent variable. This was done to control for possible effects of higher loading doses on apparent volume of distribution. Comparison of the groups was done by Student's t test for continuous variables and X2 or Fisher's exact test for categorical variables. Stepwise linear regression was performed with the use of the variables as described above. Both forward and backward stepping procedures were used and generated identical methods. A BMDP statistical package was used for all statistical analysis with 0: of
maturational process that occurs in the baseline FHR and FHR acceleration with advancing gestational age, the difference in mean gestational age of 1.9 weeks seen between the gram-positive and gram-negative groups is not great enough to account for the statistically significant difference in FHR reactivity and baseline heart rate observed between the two groupS." Because amniocentesis is invasive and difficult to perform in patients with PROM (especially those with very low fluid volume), many clinicians do not include amniotic fluid Gram stain and culture in the routine assessment of patients with preterm PROM. The diagnosis of early or subclinical chorioamnionitis, although desirable, is difficult in the absence of fever. Symptoms such as leukocytosis are quite nonspecific. The data presented here would support that the presence of fetal tachycardia (FHR > 150 beats/min) and nonreactive FHR tracing is highly suggestive of occult intraamniotic infection, and that amniocentesis to verify this suspicion is warranted. We thank Lanie M. Adamson, MS, Linda Salyer, and Elaine Baker for their assistance. REFERENCES I. Gibbs RS, Blanco jD. Premature rupture of the membranes. Obstet Gynecol 1982;60:671-9.
Gram stain results of amniocentesis
2. Garite Tj, Freeman RK, Linzy EM, Braly P. The use of amniocentesis in patients with premature rupture of membranes. Obstet Gynecol 1979;54:226-30. 3. Garite Tj. Premature rupture of membranes: the enigma of the obstetrician. AM j OBSTET GYNECOL 1985;151: 1001-5. 4. Vintzileos AM, Campbell WA, Nochimson Dj, Weinbaum Pj. Fetal breathing as a predictor of infection in premature rupture of membranes. Obstet Gynecol 1986;67: 813-7. 5. Goldstein I, Romero R, Merrill S, et al. Fetal body and breathing movements as predictors of intraamniotic infection in preterm premature rupture of membranes. AM j OBSTET GYNECOL 1988; 159:363-8. 6. Vintzileos AM, Campbell WA, Nochimson Dj, et al. The fetal biophysical profile in patients with premature rupture of membranes-an early predictor of fetal infection. AMj OBSTET GYNECOL 1985;152:510-6. 7. Vintzileos AM, Feinstein Sj, Lodeiro jG, et al. Fetal biophysical profile and the effect of premature rupture of the membranes. Obstet Gynecol 1986;67:818-23. 8. Cotton DB, Hill LM, Strassner HT, et al. Use of amniocentesis in preterm gestation with ruptured membranes. Obstet Gynecol 1984;63:38-43. 9. Gonik B, Cotton DB. The use of amniocentesis in preterm premature rupture of membranes. Am j Perinatol 1985; 2:221-4. 10. Moberg Lj, Garite Tj, Freeman RK. Fetal heart rate patterns and fetal distress in patients with preterm premature rupture of membranes. Obstet Gynecol 1984;64:60. II. Gagnon R, Campbell K, Hunse C, Patrick J. Patterns of human fetal heart rate acclerations from 26 weeks to term. AM j OBSTET GYNECOL 1987;157:743-8.
Adjusting the loading dose of magnesium sulfate for tocolysis Jeffrey W. Wright, MD, Louis E. Ridgway III, MD, and Robert M. Patterson, MD San Antonio, Texas The purpose of this prospective study was to establish a method to calculate a loading dose of magnesium sulfate so as to achieve therapeutic levels of tocolysis more quickly. Fifty patients in preterm labor were enrolled. In the first phase 25 patients were studied so that the apparent volume of distribution for the loading dose of magnesium sulfate could be estimated and an adjusted loading dose could be calculated. The efficacy of this adjusted loading dose was then tested on a further 25 patients in the second phase. We found that the apparent volume of distribution could be accurately estimated and an adjusted loading dose calculated, with the use of ideal body weight, degree of underweight, and current use of ~-sympathomimetics. In the adjusted loading dose group therapeutic levels were achieved more often, with higher postloading magnesium levels and a greater decrease in contraction index immediately after the loading dose. We conclude that an adjusted loading dose can be calculated for magnesium sulfate to optimize tocolytic therapy. (AM J OBSTET GYNECOL 1990;163:889-92.)
Key words: Magnesium, magnesium dosage, tocolytics, magnesium pharmacology
From the Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio. Presented at the Tenth Annual Meeting of the Society of Perinatal Obstetricians, Houston, Texas, January 23-27, 1990. Reprint requests: jeffrey W. Wright, MD, Department of Obstetrics and Gynecology, UTHSCSA, 7703 Floyd Curl Dr., San Antonio,
TX 78284-7836. 616122354
Magnesium sulfate is a commonly used parenteral tocolytic. It has been shown to be as effective as 13sympathomimetics with a lower incidence of serious side effects. I·' However, a longer period of time is required to achieve uterine quiescence with magnesium than with j3-sympathomimetics. 1 Several studies have demonstrated a need to achieve
889
890 Wright, Ridgway, and Patterson
September 1990 Am J Obstet Gynecol
Table I. Ideal weight table Ideal weightt (kg) Height*
Small frame
Medium frame
Large frame
4'11" 5'0" 5'1" 5'2" 5'3" 5'4" 5'5" 5'6" 5'7" 5'8"
49.8 50.9 52 53.4 54.8 56.1 57.5 58.9 60.2 61.6
54.3 55.5 56.8 58.2 59.5 60.9 62.3 63.6 65 66.4
58.9 60.2 61.6 63.2 64.8 66.4 68.0 69.5 70.7 72.5
Modified from 1983 Metropolitan life table. *Height without shoes. tWeight in patient gown.
a minimum therapeutic concentration of magnesium ions to suppress uterine activity. I. '-6 However, these levels are rarely achieved with the typical 4 grn loading dose of magnesium sulfate. 5 To achieve a therapeutic level of magnesium while avoiding potential toxicity, knowledge of the volume of distribution of magnesium is needed. However, no previous studies address the issue of the volume of distribution for the loading dose of magnesium sulfate in patients in preterm labor. The goal of this study was to establish the apparent volume of distribution of the loading dose of magnesium sulfate so that an adjusted loading dose could be calculated and to in vestigate the efficacy of this adjusted loading dose. Material and methods
In this prospective study, 50 patients admitted to the labor and delivery unit with preterm labor were enrolled. Preterm labor was defined as a gestational age of 24 to 35 weeks and regular uterine contractions accompanied by documented cervical change. Choice of tocolytic agent was by individual physician preference. In general, magnesium is used in our institution as the first-line drug for tocolysis. Patients with preexistent renal disease, suspected dehydration, or a contraindication to tocolysis were excluded. The study was done in two phases with 25 patients in each phase. In phase I patients were given a 4 gm loading dose of magnesium sulfate (MgSO,' 7H 20 United States Pharmacopeia) infused intravenously over 15 minutes with an infusion pump. Blood samples for serum magnesium determination were drawn immediately before and 1 minute after the loading dose was given. Magnesium levels were determined by means of the calmagite reaction and a Paramax System (Baxter Scientific, Irvine, Calif.). Apparent volume of distribution (AVOD) was calculated by the equa-
tion: AVOD = MgSO, loading dose [grams] X 98 [milligrams Mg+ + per gram MgSO, 1 (Postloading level - preloading level [milligrams per deciliter]) x 100 mIl dl. This formula reduced to: AVOD = 39,2001 (Postloading level-Pre loading level). Because patients in pre term labor often receive significant volumes of intravenous fluids before tocolysis AVOn was corrected by the following equation: True AVOD = Measured AVOD - (Intravenous fluidsUrine output). For each patient, height, weight, ideal body weight, degree of weight over or under the ideal, gestational age, body surface area, presence of multiple gestation, previous exposure to magnesium, and current therapy with [3-sympathomimetic tocolytics were recorded. Ideal body weight was estimated by a modified 1983 Metropolitan life table. This table was generated by taking the midpoint of the range of ideal weight for a given height and frame size, converting it to kilograms, and correcting for lack of shoes and clothing (Table I). For overweight patients, overweight was calculated by: Overweight = Actual weight - Ideal weight. For underweight patients underweight was calculated by: Underweight = Ideal weight - Actual weight. Contraction monitor strips for 30 minutes before the loading dose began and 30 minutes after completion were photocopied for future analysis. After completion of the study, two blinded examiners scored the monitor strips for contraction index and number of contractions in 30 minutes. The contraction index was calculated as the total duration of contractions during 30 minutes of monitoring. Stepwise linear regression was used to establish the relationship between apparent volume of distribution and the independent variables weight, ideal weight, underweight, overweight, body surface area, multiple gestation, previous exposure to magnesium, and current therapy with [3-sympathomimetics. In phase 2, apparent volume of distribution was estimated by the equation established in phase 1: AVOn = 613.1 + 215.7 (Ideal weight in kilograms) + 408.3 (Underweight in kilograms) - 2182.7 (ifreceiving [3-sympathomimetic). The adjusted loading dose was calculated by this equation: Loading dose = AVOD [milliliters] X 5.2 [Expected change in serum Mg+ +] 1 (98 [milligrams Mg+ + per gram MgSO,] X 100 [milligrams per deciliter]). The simplified equations are shown in Table II. We assumed an approximate baseline level of 1.8 mg/dl and target level of 7 mg/dl. The minimum therapeutic level was.defined as 6 mg/dl. Magnesium infusion technique, as well as other treatment and data collection, was identical to that of phase 1. After phase 2 was completed, stepwise linear regression was again performed with study phase added as
Adjusting loading dose of magnesium
Volume 163 Number 3
Table II. Calculation of the adjusted loading dose Apparent volume of distribution = 613.1 + 215.7 (Ideal weight, kilograms) + 408.3 (Underweight, kilograms) - 2182.7 [If receiving 13sympathomimetic] Adjusted loading dose [grams] = 0.00053 x Apparent volume of distribution
*Appropriate safety precautions should be observed during
magnesium infusion.
an independent variable. This was done to control for possible effects of higher loading doses on apparent volume of distribution. Comparison of the groups was done by Student's t test for continuous variables and X2 or Fisher's exact test for categorical variables. Stepwise linear regression was performed with the use of the variables as described above. Both forward and backward stepping procedures were used and generated identical methods. A BMDP statistical package was used for all statistical analysis with 0: of
