The Treatment of Preterm Labor Using a Portable Subcutaneous Terbutaline Pump

Transcription

1 The Treatment of Preterm Labor Using a Portable Subcutaneous Terbutaline Pump D. JEAN SALA, RN, MSN, AND KENNETH J. MOISE, JR., MD The perinatal mortality rate related to preterm delivery has led researchers to investigate new methods of tocolysis. A new concept in managing preterm labor uses continuous administration of terbutaline sulfate via a portable subcutaneous infusion pump. Use of the terbutaline pump to treat 13 preterm labor patients at the Baylor College of Medicine demonstrated an efficacy rate of 9 for a population failing all other methods of tocolysis. This unique treatment modality offers new hope for patients experiencing recalcitrant preterm labor. Preterm labor is the single most common cause of prematurity.' The perinatal morbidity rate related to preterm delivery has led researchers to investigate new methods of tocolysis. During the past 20 years, several drugs, including ethanol, magnesium sulfate, and a variety of betamimetic agents, have been used with only marginal success for treating preterm labor. Prostaglandin inhibitors, calcium channel blockers, and oral magnesium also have been tried with essentially the same marginal success.* A new method of tocolysis that uses continuous delivery of terbutaline sulfate via a portable subcutaneous infusion pump has shown promise for managing recalcitrant preterm labor.3 When used judiciously in a carefully screened population, the terbutaline pump can be useful in managing preterm labor.4 PHARMACOKINETICS Terbutaline sulfate is a member of a drug class known as beta-adrenergics. Adrenergic drugs are sympathetic amines that affect adrenergic receptor Accepted: May 1989 sites to varying degrees, depending on the drug. Adrenergic activity can be selectively inhibited through two different cellular receptor sites classified as alpha and beta. The interaction of catecholamine with the alpha receptor sites causes the uterus to contract. Conversely, interaction with beta receptor sites leads to uterine relaxation. Beta-adrenergic receptor sites are further classified into beta-one and beta-two. Beta-one receptor site responses include inotropic effects, which relate to the force of cardiac contraction, and chronotropic effects, which relate to the rate of cardiac contractions. Additionally, beta-one site responses stimulate relaxation of the smooth muscle of the intestine and increase the rate of lipolysis. Stimulation of beta-two receptor sites leads to relaxation of the smooth muscles of the uterus, arterioles, and bronchi; glycogenolysis in the liver and muscle; and insulin release.* DRUG-RELATED SIDE EFFECTS AND COMPLICATIONS Tocolytic drugs capable of stimulating only betatwo receptor sites are not available.2 Therefore, adverse side effects are separated into beta-one and beta-two responses. Beta-one side effects primarily are increased heart rate, increased cardiac contrac :2 March/April 1990 JOCNN

2 tility, and lipolysis. Beta-two side effects include tachycardia, palpitations, tremors, and nervousness. Beta-two side effects essentially are dose related. As the dose of a betamimetic increases, a loss of selectivity occurs, which leads to side effects resembling those of epinephrine. Epinephrine stimulates both beta-one and beta-two receptor sites and, therefore, may produce side effects similar to those described previously. I A continuous low-dose infusion of terbutaline is thought to result in less desensitization of receptor sites. To reduce the number and severity of side effects related to terbutaline, the dosage must be low. However, in the traditional method of administration, terbutaline is given intravenously or subcutaneously, requiring that the patient be hospitalized, often receiving considerably high levels of medication and suffering an increased number of side effects. The oral route of administration also is used, but the regimen is associated with a high recurrence rate of preterm labor and the need for the patient to be readmitted to the hospital. A continuous low-dose infusion of terbutaline is thought to result in less desensitization of receptor sites. This phenomenon is also known as down-regulati~n.~ Similar responses often are encountered by a patient using narcotics for pain control. As the time period of drug use increases, the effect on pain management decreases, assuming the amount of medication being administered remains constant. Consequently, after a prolonged period of time, terbutaline will become less effective. MUSCLE PHYSIOLOGY AND UTERINE ACTIVITY PATTERNS The rationale for using terbutaline is easy to understand on the basis of cellular physiology. Uterine muscle cells require calcium to contract. Calcium, which is stored in high concentrations outside the cell, enters the cell when the electronic potential of the cell membrane changes. Uterine relaxation is dependent on calcium being pumped out of the cell. The calcium pump depends on cyclic adenosine monophosphate (AMP) and the enzyme adenylate cyclase, which acts on the calcium pump and causes calcium to leave the cell. Without high intracellular levels of calcium, the muscle relaxes.' Terbutaline stimulates the beta receptors and activates adenylate cyclase, causing the active transport of calcium out of the myometrial cell. This cascade of events causes uterine relaxation to occur.' Two types of uterine activity are known: uterine irritability and regular organized contractions that Figure 1. Uterine irritability before pump therapy. 192 March/April 1990 JOGNN 109

3 are appreciated by the patient. Uterine irritability can be described as high-frequency, low-intensity contractions and is thought to be a precursor to actual preterm labor? Regular organized contractions are characterized by low-frequency, high-intensity uterine activity. Continuous external tocodynamometer monitoring during initiation of pump therapy assists the healthcare provider to ascertain the various types of uterine activity the patient is experiencing. With this information, uterine activity patterns can be identified and appropriate pump therapy provided. Figures 1 and 2 illustrate uterine irritability and regular contractions demonstrated by a stabilized patient who was placed on terbutaline pump therapy. Figure 3 illustrates the dramatic effect that can be achieved with pump therapy, as noted by the absence of uterine irritability or' regular contractions. PUMP CANDIDATE SELECTION A portable external infusion pump, originally designed for insulin administration, was modified to accommodate terbutaline sulfate administration to those pregnant women in the original series of patients who were experiencing preterm labor.3 The pump is small, easy to operate, and portable and, thus, is well suited for institutional and home use. However, because of health-care practitioners' relative lack of experience in using the pump for preterm labor, the pump should be reserved for use only after all other methods have failed. The following clinical considerations should be reviewed when selecting a patient for pump therapy: 1) fetus' gestational age between 20 and 35 weeks: 2) preterm labor diagnosis based on recorded uterine activity: 3) cervical dilation less than 4 cm; 4) stabilized preterm labor (preferably with intravenous magnesium sulfate therapy): 5) estimated fetal weight of less than 2,500 g; 6) intact fetal membranes with no bulging through the cervical 0s: 7) viable fetus; and 8) patient has no medical contraindications to betamimetic agents (i.e., cardiovascular disease, diabetes mellitus, or history of migraine headache^).^ I The pump is small, easy to operate, and portable and, thus, is well suited for institutional and home use. Because preterm labor is a high-risk complication of pregnancy and terbutaline pump therapy is a new treatment modality, a maternal-fetal specialist skilled in the use of the pump should be consulted for guidance in patient care. Figure 2. Regular uterine contractions before pump therapy :2 March/April 1990 JOG"

4 Figure 3. Uterine quiescence following initiation of pump therapy. Patient Assessment before Pump Therapy Before starting pump therapy, the patient must be hospitalized and stabilized with a regimen of intravenous magnesium sulfate. Since terbutaline can potentially alter many metabolic and cardiovascular functions, the following studies should be performed to enable the health-care provider to establish that pump therapy will not jeopardize the patient s condition: 1) a thorough physical examination; 2) a complete blood count with differential, serum electrolytes and glucose to evaluate the patient for the presence of anemia, infection, electrolyte imbalance, or carbohydrate intolerance; 3) a cervical gram stain and culture and sensitivity using selective media to identify Neisseria gonorrhea, Chlamydia trachomatis, or group B streptococci; and 4) a baseline electrocardiogram to establish normal cardiac function. Understanding the Pump Settings Three basic modes for medication administration can be programmed into the pump: basal rate, bolus dose, and profile mode. The basal rate delivers a continuous low dose of terbutaline at a set rate. This mode of therapy is most effective in treating uterine irritability, which often occurs in the early morning. The bolus dose delivers a larger quantity of medication to treat regular organized contractions, which often occur more frequently in the evening. The profile mode enables the pump to be preset to deliver automatically a bolus dose during times that uterine contractions regularly occur. This mode is particularly beneficial when organized contractions regularly occur during normal sleep periods. This enables the patient to rest quietly without the inconvenience of waking to take needed medi~ation.~ Initiation of Pump Therapy A variety of methods can be used to initiate pump therapy. The method depends on the patient s stability and the length of time she has been receiving betamimetic drugs to control preterm labor. If the patient has been receiving large doses of betamimetic agents, such therapy should be discontinued during this time. Intravenous magnesium sulfate therapy is required for tocolysis during this time for approximately hours. This practice is aimed toward desensitizing the patient s receptor sites to enhance the effectiveness of pump the rap^.^ Laboratory values, such as serum electrolytes, obtained during this time can be expected to be within normal limits. If the patient is receiving only magnesium sulfate for tocolysis, the transition requires only a gradual decrease in the rate of administration until the patient is stable 192 MarchlApril 1990 JOGNN 111

5 ~ a on the pump therapy alone. Generally, the magnesium sulfate should be decreased by one-half gram per 12-hour peri~d.~ Because preterm labor is a high-risk complication of pregnancy and terbutaline pump therapy is a new treatment modality, maternal-fetal specialist skilled in the use of the pump should be consulted for guidance in patient care. The basal rate generally is started at.05 mg/hour and adjusted accordingly. Alterations are made depending on the degree and frequency of uterine irritability that the patient is experiencing. The maximum basal rate should not exceed.10 mg/hour. The bolus dose for the treatment of regular organized contractions is.25 mg/hour. This dose is not to be increased and should not be administered if the patient s pulse rate exceeds 110 beats per minute. Additionally, the patient should not receive more than five to seven boluses per day. Changing Pump Settings Often during pump therapy, alterations in the basal rate or timing of bolus doses may be necessary. If prolonged uterine irritability should occur, the basal rate may be increased. Caution is advised, however, because of the occurrence of down-regulation or desensitization associated with higher doses of betamimetics.4 The lower the dose of terbutaline, the less chance of rebound uterine activity. As a general rule, regular organized contractions occurring in greater frequency than four per hour require a one-time bolus. However, under certain circumstances, with physician approval and a pulse rate less than 110 beats per minute, the patient may receive a maximum of three boluses over a one-hour period for persistent contractions. If this regimen does not relieve the contractions, hospitalization should be considered. Occasionally, some patients may have more than four contractions per hour on a regular basis, which may be their individual base line uterine activity; therefore, they may not need frequent bolus doses. The key to managing these patients is the presence or absence of cervical change related to the contractions. Weekly cervical examinations performed in the office or in the home by the physician or a specially trained perinatal nurse will assist the health-care team in identifying cervical change related to uterine activity. I Before starting pump therapy, the patient must be hospitalized and stabilized with a regimen of intravenous magnesium sulfate. PATIENT EDUCATION Patient education ideally should start as soon as the patient enters the hospital. Instruction should be provided by nurses or other health-care providers with adequate training and experience regarding the pump s use in preterm labor treatment. Because the stress of preterm labor and hospitalization may affect patient learning, training should be provided in short sessions. During the first session, the health-care provider can be instrumental in setting realistic expectations, as well as answering the patient s questions regarding pump therapy. This is the time to discuss basic concepts of pump therapy, patient responsibilities, and the importance of strict bed rest. Information should be provided regarding how to wear the pump, accessories used, home uterine monitoring basics, and follow-up care.5 I Because the stress of preterm labor and hospitalization may affect patient learning, training should be provided in short sessions. Self-Administration Using the Pump The second session is reserved for hands-on practice with the pump and therapy initiation. During this session, the patient is instructed on how and when to take her pulse, load the syringe, prime the tubing, and insert the needle. Information about care of the needle site, changing the pump batteries, and how to wear the pump also is provided at this time.5 Figures 4-7 illustrate some of the basic skills required for terbutaline pump therapy. The third session is a formal review session when the patient demonstrates everything she has learned. The health-care provider can evaluate the patient s technique, correct any problem, and answer any further questions. Home Uterine Monitoring The final session is devoted to home uterine monitoring. Since terbutaline pump therapy is dependent :2 March/April 1990 JOCNN

6 lysis with oral indomethacin or intravenous magnesium sulfate to maintain uterine quiescence. In four of the patients, the terbutaline pump was considered unsuccessful because of persistent elevations of the maternal pulse or irregular maternal heart beats. One patient, who was extremely anxious before pump therapy, requested to be taken off the pump because of tremors she attributed to terbutaline pump therapy. CASE STUDIES The following two case studies demonstrate that, although the terbutaline pump often is useful in controlling preterm labor in patients when all other methods have failed, pump therapy is not without risk. Case 1 Figure 4. Drawing up the terbutaline sulfate. on identification of specific types of uterine activity, outpatient uterine monitoring is essential. A variety of home health-care agencies now provide this service, and some are offering a terbutaline pump service to facilitate ambulatory care of pump-therapy patients. DISCUSSION During our experience, 13 patients with excessive uterine activity and documented cervical changes were referred for trials of terbutaline pump therapy. Of those 13 patients, 5 were receiving oral terbutaline in large doses, and 4 were receiving oral indomethacin and terbutaline. Additionally, 2 patients were receiving intravenous magnesium sulfate on the antepartum unit. Those patients receiving terbutaline were placed on a regimen of intravenous magnesium sulfate for hours before initiation of pump therapy. Patients were then started on pump therapy. The patients ranged from 21 to 33 weeks' gestation at the time of referral. Eight patients were singleton pregnancies, two patients were pregnant with triplets, and one patient was carrying twins. Of the 13 cases, three patients were successfully treated solely with the pump. Six patients required additional toco- M., a gravida 4, para 0, had experienced preterm labor with documented cervical change since 23 weeks' gestation. Treatment with oral terbutaline was only marginally successful. By 28 weeks' gestation, M. was on a regimen of 7.5 mg of oral terbutaline every two hours with continued frequent contractions and numerous hospitalizations. After all physical and laboratory data revealed no contraindications to pump therapy, M. was started on a regimen of a basal rate of.05 mg/hour with bolus doses of.25 mg scheduled as needed for more than four contractions per hour. During the next two days, M.'s basal rate was increased to.07 mg/hour and later increased to.09 mg/hour. M. was discharged home four days later and was followed as an outpatient, with the exception of a two-day hospitalization occurring two weeks Figure 5. Skin preparation by patient before inserting the infusion needle. 192 March/April 1990 JOG" 113

7 dysrhythmias noted by holter monitoring during pump therapy. NURSING IMPLICATIONS Figure 6. Inserting the needle. after initiation of pump therapy. During M. s readmission to the hospital, regular organized contractions that did not adequately resolve with pump therapy were noted to occur every three to four minutes. The patient was, therefore, placed on additional tocolysis consisting of 25 mg of oral indomethacin every six hours for one week. No further episodes of regular organized contractions were noted following discontinuation of indomethacin, and M. remained stable on pump therapy alone. The terbutaline pump was discontinued at 37 weeks gestation. M. delivered a healthy female neonate one week later. Case 2 F., a gravida 2, para 1, had experienced preterm labor with her first pregnancy and ultimately delivered a stillborn infant at 32 weeks gestation. Her second pregnancy was with twins and also was complicated by preterm labor beginning at 21 weeks gestation. After oral terbutaline, indomethacin, and intravenous magnesium sulfate therapies failed to adequately control her contractions, F. was started on terbutaline pump therapy. The pump worked well to control her uterine activity; however, nine days after initiation of the pump therapy, F. reported feeling skipped heartbeats. Holter monitoring later revealed evidence of frequent preventricular contractions with occasional bursts of bigeminy. Because of the potential risk of further cardiovascular complications, pump therapy was discontinued. F. was maintained on a regimen of intravenous magnesium sulfate for tocolysis. At periodic intervals, F. required short-term administration of oral indomethacin or intravenous narcotics for sedation to treat exacerbations of organized contractions. At 35 weeks gestation, preterm labor ensued that did not respond to tocolysis. F. ultimately delivered healthy twin female neonates. Figure 8 illustrates the Terbutaline pump therapy is emerging as an acceptable alternative to traditional methods for treating preterm labor. Perinatal nurses must possess the knowledge and skills required to adequately care for these patients. The patient often looks to the nurse to answer questions related to pump therapy. Therefore, nurses also must thoroughly understand the operations of the pump and be skilled in providing patient education. Selecting suitable patients for pump therapy relies on thoroughly assessing each patient s condition. Competency in performing physical assessments is critical. The abilities to identify adventitious heart and lung sounds, as well as interpret fetal heart rate patterns and tocodynamometry, are particularly important. Determining the efficacy of pump therapy requires excellent skills in assessing cervical dilation, effacement, station, and consistency. Once the patient is home, the home-bound perinatal nurse also must be capable of performing a thorough physical assessment, as well as conducting nutritional and psychosocial evaluations. CONCLUSION Much remains to be learned about preterm labor and its treatment. The terbutaline pump offers hope as a new tocolytic regimen for recalcitrant preterm labor. In our experience with a total of 13 patients in active preterm labor with documented cervical change, pump therapy was discontinued in 4 patients because of mild cardiovascular complications, such Figure 7. Programming the pump :2 March/April 1990 JOGNN

8 Figure 8. Preventricular contractions during administration of terbutaline sulfate by continuous subcutaneous pump. as sustained tachycardia or frequent preventricular contractions. This yielded an overall efficacy rate of 9 patients who had failed all other methods of tocolysis. However, the failure rate of 4 patients, due to mild cardiovascular complications necessitating discontinuation of pump therapy, also was noted. Therefore, patients considered for pump therapy must be thoroughly evaluated and alternative therapies applied whenever possible. For patients who meet the criteria, the terbutaline pump may offer an alternative treatment that could make a difference in terms of perinatal outcome. REFERENCES 1. Converse, J Care of the patient receiving therapy with betamimetic agents. Wis Med J. 82: Creasy, R., and R. Resnik Maternal-Fetal Medicine: Principals and Practice. Philadelphia: W.B. Saunders, pp. 421, Lam, F., P. Gill, M. Smith, J. Kitzmiller, and M. Katz Use of the subcutaneous terbutaline pump for long-term tocolysis. Obstet Gynecol. 72(5): Lam, F Miniature pump infusion of terbutaline: An option in preterm labor. Contemporary OB/GYN. 33(1): Lam, F., and P. Gill Terbufaline Pump Therapy Guide. Sylmar, California: MiniMed Technologies, pp. 3, Guyton, A Textbook of Medical Physiology. Philadelphia: W.B. Saunders, p Cotton, D., H. Strassner, L. Lipson, et al The effects of terbutaline on acid base, serum electrolytes and glucose homeostasis during the management of preterm labor. A-m J Obstet Gynecol. 141(6): Gill, P., M. Smith, and C. McGregor Terbutaline by pump to prevent recurrent preterm labor. MCN. 14(3). Address for correspondence: D. Jean Sala, RN, MSN, 8723 Ashkirk, Houston, TX D. Jean Sala is a perinatal clinical nurse specialist and adjunct graduate-level faculty member for the University of Texas, School of Nursing, in the High-Risk Perinatal Tract. Ms. Sala,also works as a staff nurse and relief assistant nurse manager at St. Luke's Episcopal Hospital in Houston. Ms. Sala is a member of NAACOG, the American Nurses' Association, and Sigma Theta Tau. Kenneth J. Moise, Jr., is an assistant professor in the Department of Obstetrics and Gynecology. Division of Maternal-Fetal Medicine, at Baylor College of Medicine in Houston, Texas. Dr. Moise is a member of the American College of Obstetricians and Gynecologists, the American Medical Association, and the Society of Perinatal Obstetricians. 19:2 March/April 1990 JOGNN 115