- Email: [email protected]
Milrinone use in the pregnant ewe
Volume 167 Number 4, Part 1
2. Leferink ]G, Lamont H, Wagemaker-Engels RA, et al. Pharmacokinetics of terbutaline after subcutaneous administration. Int ] Clin Pharmacol Biopharm 1979; 17: 181-5. 3. Ryden G, Rolf G, Andersson G, et al. Is the relaxing effect of j3-adrenergic agonists on the human myometrium only transitory? Acta Obstet Gynecol Scand Suppl 1982; 108:4751. 4. Valenzuela G, Cline S. Use of magnesium sulfate in premature labor that fails to respond to j3-mimetic drugs. AM ] OSSTET GYNEcoLl982;143:718-9. Reply To the Editors: It is an honor to respond to Lam's letter. Without his help, our beautiful and brilliant little boy would not have achieved the 35 weeks of gestation that he did. My wife was one of the first handful of women managed with subcutaneous terbutaline infusion therapy by Lam and Pamela Gill, RN. I make this personal reference to underscore the critical importance of prolonging pregnancy and preventing premature delivery. The consequences of prematurity remain the greatest risk facing any expecting couple. The subcutaneous terbutaline infusion pump is in our opinion an extremely important development in obstetric care because of its success in achieving long-term tocolysis. For this reason, the presented case report is of great significance and the opportunity to more thoroughly explore its content is appreciated. Many of the questions raised by Lam are similar to those asked by Bey et al. l Although the daily contraction records are unavailable, the tocolytic infusion was titrated on the basis of uterine activity. Unfortunately, the patient summaries indicate that uterine activity was poorly controlled and was responsible for the escalation of the terbutaline infusion rate. At office visits the fetal heart rate was reported to be within normal limits; however, maternal tachycardia was present and the patient was highly symptomatic. Ultimately the subcutaneous terbutaline infusion was discontinued at 36 weeks because of maternal jitteriness and tachycardia. Because we were not responsible for the obstetric care of this patient, we are uncertain as to whether either intravenous magnesium sulfate or amniocentesis were considered when recurrent preterm labor occurred. These would seem to be reasonable alternatives when confronted with the need for such significant increases in the terbutaline dosage. The patient also had class AI diabetes. A glucola screen was elevated at 145 mg/dl and the follow-up 3-hour oral glucose tolerance test was abnormal. After beginning a 2000-calorie / day American Diabetes Association diet, all follow-up fasting and 2-hour postprandial blood sugar levels were <100 mg/dl. There was no polyhydramnios, macrosomia, or neonatal hypoglycemia that I would associate with a possible fetal diabetic cardiomyopathy. We have had extensive experience with subcutaneous terbutaline infusion and have not had similar neonatal problems. However, in vitro evidence suggests a potential for fetal cardiac toxicity,2.3 and other cases have been reported! We agree with Lam that either the ex-
Letters
1157
cessive dosage of subcutaneous terbutaline or the longer duration of fetal exposure may have contributed to the adverse cardiovascular effects seen in this neonate. More study needs to be done on this new and potentially valuable tocolytic delivery system; in the meantime, careful attention should be given to the treatment recommendations outlined by Lam. 5 Roger B. Newman, MD Medical University of South Carolina, 171 Ashley Ave., Charleston,
SC 29425
REFERENCES
1. Bey M, Blanchard AC, Darnell], Stephens K. Myocardial necrosis in a newborn after long-term maternal subcutaneous terbutaline for suppression of premature labor [Letter]. AM] OSSTET GYNECOL 1992;167:292. 2. Peterson R, Carter LS, Chescheir NC, et al. Effects of terbutaline sulfate on fetal cardiac function. AM ] 011 STET GYNECOL 1989;161:509-12. 3. Dagbjartsson A, Herbertsson G, Stefansson TS, et al. Betaadrenergic agonist and hypoxia in sheep fetuses. Acta Physiol Scand 1989;137:291-9. 4. Thorkelsson T, Loughead] L. Long-term subcutaneous terbutaline tocolysis: report of possible neonatal toxicity. J Perinatol 1991;11:235-8. 5. Lam F, Gill P, Smith M, Kitzmiller ]L, Katz M. Use of the subcutaneous terbutaline pump for long-term tocolysis. Obstet Gynecol 1988;72:810.
Milrinone use in the pregnant ewe To the Editors: I read with interest the article by Santos et al. (Santos AC, Baumann AL, Wlody D, Pedersen H, Morishima HO, Finster M. The maternal and fetal effects of milrinone and dopamine in normotensive pregnant ewes. AM J OBSTET GYNECOL 1992;166:257-62). Their findings of no adverse effects on the pregnant ewe or fetus are encouraging, and hopefully milrinone will be useful in the care of the critically ill pregnant woman who requires inotropic support. However, as of this writing, milrinone, although approved for release by the Food and Drug Administration, has not been released by Winthrop Labs. As such, it is unavailable to the intensivist. Amrinone is an inotrope with similar effect. The first use of amrinone in human pregnancy was recently described by me. I Although cardiac output increased and systemic vascular resistance decreased, metabolic acidosis, hypoxemia, and premature ventricular complexes developed. Fetal monitoring was limited to external heart rate monitoring, with no obvious changes occurring. Until milrinone is available and experience using it is gained, for the gravid woman who requires inotropic support, amrinone may be a better choice in spite of these adverse effects on one patient. Russel D. Jelsema, MD Department of Obstetrics and Gynecology, Butterworth Hospital, 100 Michigan NE, Grand Rapids, MI49503
REFERENCE 1. ]elsema RD,Bhatia RK, Ganguly S. Use of intravenous amrinone in the short-term management of refractory heart failure in pregnancy. Obstet GynecoI1991;78:935-6.
2. Leferink ]G, Lamont H, Wagemaker-Engels RA, et al. Pharmacokinetics of terbutaline after subcutaneous administration. Int ] Clin Pharmacol Biopharm 1979; 17: 181-5. 3. Ryden G, Rolf G, Andersson G, et al. Is the relaxing effect of j3-adrenergic agonists on the human myometrium only transitory? Acta Obstet Gynecol Scand Suppl 1982; 108:4751. 4. Valenzuela G, Cline S. Use of magnesium sulfate in premature labor that fails to respond to j3-mimetic drugs. AM ] OSSTET GYNEcoLl982;143:718-9. Reply To the Editors: It is an honor to respond to Lam's letter. Without his help, our beautiful and brilliant little boy would not have achieved the 35 weeks of gestation that he did. My wife was one of the first handful of women managed with subcutaneous terbutaline infusion therapy by Lam and Pamela Gill, RN. I make this personal reference to underscore the critical importance of prolonging pregnancy and preventing premature delivery. The consequences of prematurity remain the greatest risk facing any expecting couple. The subcutaneous terbutaline infusion pump is in our opinion an extremely important development in obstetric care because of its success in achieving long-term tocolysis. For this reason, the presented case report is of great significance and the opportunity to more thoroughly explore its content is appreciated. Many of the questions raised by Lam are similar to those asked by Bey et al. l Although the daily contraction records are unavailable, the tocolytic infusion was titrated on the basis of uterine activity. Unfortunately, the patient summaries indicate that uterine activity was poorly controlled and was responsible for the escalation of the terbutaline infusion rate. At office visits the fetal heart rate was reported to be within normal limits; however, maternal tachycardia was present and the patient was highly symptomatic. Ultimately the subcutaneous terbutaline infusion was discontinued at 36 weeks because of maternal jitteriness and tachycardia. Because we were not responsible for the obstetric care of this patient, we are uncertain as to whether either intravenous magnesium sulfate or amniocentesis were considered when recurrent preterm labor occurred. These would seem to be reasonable alternatives when confronted with the need for such significant increases in the terbutaline dosage. The patient also had class AI diabetes. A glucola screen was elevated at 145 mg/dl and the follow-up 3-hour oral glucose tolerance test was abnormal. After beginning a 2000-calorie / day American Diabetes Association diet, all follow-up fasting and 2-hour postprandial blood sugar levels were <100 mg/dl. There was no polyhydramnios, macrosomia, or neonatal hypoglycemia that I would associate with a possible fetal diabetic cardiomyopathy. We have had extensive experience with subcutaneous terbutaline infusion and have not had similar neonatal problems. However, in vitro evidence suggests a potential for fetal cardiac toxicity,2.3 and other cases have been reported! We agree with Lam that either the ex-
Letters
1157
cessive dosage of subcutaneous terbutaline or the longer duration of fetal exposure may have contributed to the adverse cardiovascular effects seen in this neonate. More study needs to be done on this new and potentially valuable tocolytic delivery system; in the meantime, careful attention should be given to the treatment recommendations outlined by Lam. 5 Roger B. Newman, MD Medical University of South Carolina, 171 Ashley Ave., Charleston,
SC 29425
REFERENCES
1. Bey M, Blanchard AC, Darnell], Stephens K. Myocardial necrosis in a newborn after long-term maternal subcutaneous terbutaline for suppression of premature labor [Letter]. AM] OSSTET GYNECOL 1992;167:292. 2. Peterson R, Carter LS, Chescheir NC, et al. Effects of terbutaline sulfate on fetal cardiac function. AM ] 011 STET GYNECOL 1989;161:509-12. 3. Dagbjartsson A, Herbertsson G, Stefansson TS, et al. Betaadrenergic agonist and hypoxia in sheep fetuses. Acta Physiol Scand 1989;137:291-9. 4. Thorkelsson T, Loughead] L. Long-term subcutaneous terbutaline tocolysis: report of possible neonatal toxicity. J Perinatol 1991;11:235-8. 5. Lam F, Gill P, Smith M, Kitzmiller ]L, Katz M. Use of the subcutaneous terbutaline pump for long-term tocolysis. Obstet Gynecol 1988;72:810.
Milrinone use in the pregnant ewe To the Editors: I read with interest the article by Santos et al. (Santos AC, Baumann AL, Wlody D, Pedersen H, Morishima HO, Finster M. The maternal and fetal effects of milrinone and dopamine in normotensive pregnant ewes. AM J OBSTET GYNECOL 1992;166:257-62). Their findings of no adverse effects on the pregnant ewe or fetus are encouraging, and hopefully milrinone will be useful in the care of the critically ill pregnant woman who requires inotropic support. However, as of this writing, milrinone, although approved for release by the Food and Drug Administration, has not been released by Winthrop Labs. As such, it is unavailable to the intensivist. Amrinone is an inotrope with similar effect. The first use of amrinone in human pregnancy was recently described by me. I Although cardiac output increased and systemic vascular resistance decreased, metabolic acidosis, hypoxemia, and premature ventricular complexes developed. Fetal monitoring was limited to external heart rate monitoring, with no obvious changes occurring. Until milrinone is available and experience using it is gained, for the gravid woman who requires inotropic support, amrinone may be a better choice in spite of these adverse effects on one patient. Russel D. Jelsema, MD Department of Obstetrics and Gynecology, Butterworth Hospital, 100 Michigan NE, Grand Rapids, MI49503
REFERENCE 1. ]elsema RD,Bhatia RK, Ganguly S. Use of intravenous amrinone in the short-term management of refractory heart failure in pregnancy. Obstet GynecoI1991;78:935-6.