Rhabdomyolysis caused by tocolytic therapy with oral ritodrine hydrochloride in a pregnant woman with placenta previa

Oral-ritodrine-hydrochloride-induced rhabdomyolysis is rare. We report a case of oral-ritodrine-hydrochloride-induced rhabdomyolysis in a pregnant woman with placenta previa without neuromuscular disorders. The patient was a 30-year-old, Japanese primigravida woman, who became pregnant spontaneously. At 23 gestational weeks, she was diagnosed as having placenta previa and prophylactic oral ritodrine hydrochloride (15 mg/day) was initiated. At 29 1/7 gestational weeks, she was referred to our hospital for perinatal management of placenta previa. Two days thereafter, vaginal bleeding accompanied by frequent uterine contractions occurred and she was admitted. On admission, laboratory tests revealed an abnormal increase of blood creatine kinase (CK) value of 7200 IU/L. CK-MB isoenzyme was 208 IU/L. Aspartate transaminase (163 IU/L), alanine transaminase (74 IU/L) and lactate dehydrogenase (536 IU/L) levels were also increased. The patient started to complain of extreme muscle pain in her upper and lower limbs and general weakness. The next day, laboratory tests revealed a tremendous increase of blood CK level of 87,300 IU/L, a blood myoglobin level of 11,200 ng/mL, and a urinary myoglobin level of 615 ng/mL. An emergency cesarean section was carried out. After delivery, the laboratory data improved gradually with the CK levels at 107 IU/L. If patients complain of muscular symptoms following oral ritodrine hydrochloride use, physicians should consider rhabdomyolysis.     

A loading-dose infusion scheme for intravenous tocolysis with ritodrine: a pilot study

A loading-dose infusion scheme for intravenous ritodrine therapy was tested in twelve patients with preterm labour. We started with a rather high (386 micrograms/min) infusion rate, but the moment tocolysis was reached this infusion rate was reduced to a level needed to maintain the plasma concentration then found. Plasma samples of ritodrine were taken the moment tocolysis was reached and in the steady state, and compared with each other and with expected and calculated plasma concentrations. In the dynamic loading phase we found a half-life for ritodrine of 1 h. This half-life of 1 h can be explained by cumulation of ritodrine in the central compartment and is therefore called cumulation t1/2. In developing an infusion scheme with a loading dose for ritodrine, this cumulation t1/2 of 1 h should be taken into account.     

Cardiac and uterine hemodynamic responses to ritodrine hydrochloride administration in pregnant sheep.

The changes in the maternal circulation following administration of ritodrine hydrochloride were investigated in chronically prepared pregnant sheep. Low infusion rates of ritodrine (see text) elevated the maternal heart rate and cardiac output and decreased peripheral vascular resistance. Stroke work fell while minute work increased. The distribution of uterine blood flow did not change, as measured with microspheres. Simultaneously measured fetal cardiac output and umbilical blood flow were not altered. When ritodrine infusion rates (see text) were increased there was a slight but significant decrease in uterine perfusion pressure, and an increase in uterine vascular resistance with uterine blood flow decreasing. These changes were observed when the ewes were not in labor, and similar changes were again recovered with ewes in labor despite the simultaneous inhibition of uterine contractions. Selective beta blockade with practolol during ritodrine administration decreased the maternal tachycardia without affecting cardiac output, peripheral vascular resistance, or uterine vascular resistance.     

Acute coronary syndrome associated with oral administration of ritodrine hydrochloride during pregnancy: a case report.

We report a case of acute coronary syndrome associated with the oral administration of ritodrine hydrochloride. Ten days following the administration of ritodrine hydrochloride, the patient complained of chest pain, and an electrocardiogram showed ST elevation and ST depression. Intensive care was initiated. She recovered without chest pain.     

A prospective randomized trial of acute tocolysis in term labour with atosiban or ritodrine

OBJECTIVE: To study the effects of the tocolytics atosiban and ritodrine in term labour. STUDY DESIGN: Women in term labour, requiring acute tocolysis, were prospectively randomized for treatment with either atosiban i.v. (n=70) or ritodrine i.v. (n=70). There were three indications for acute tocolysis: (1) fetal distress followed by continuation of labour, (2) fetal distress followed by emergency caesarean section (CS), and (3) arrest of contractions in women waiting for a secondary CS in the absence of fetal distress. Primary endpoints were maternal blood pressure (MBP) and maternal heart rate (MHR). Secondary endpoints were intra-uterine pressure, fetal heart rate (FHR), 5'-Apgar score and umbilical arterial pH. RESULTS: Baseline characteristics did not differ between the study groups. The ritodrine group showed a significant rise in MHR (p<0.001), MHR remained unaltered in the atosiban group (p=0.31). No significant changes occurred in systolic and diastolic BP in either group. FHR rose by a maximum of 11.6 bpm (8.5%) in the ritodrine group (p<0.001) compared to a rise of 4.9 bpm (4.8%) in the atosiban group (p=0.27). No differences were found in blood loss and fetal outcome. Compared to baseline, uterine pressure was reduced by a maximum of 55% (p<0.001) after ritodrine administration, compared to a maximal reduction of 54% (p<0.001) after atosiban administration. These effects did not differ between the two treatment groups. CONCLUSION: Considering the maternal effects, our results suggest a possible role for atosiban bolus in acute tocolysis in term labour.     

Metabolism and disposition of ritodrine in a pregnant baboon

Relatively little is known about the detailed metabolism of ritodrine. The aim of this study was to examine ritodrine metabolism and pharmacokinetics in the maternal and fetal baboon. A fetal-maternal model was made with use of Papio anubis at 144 days of gestation. Tritiated ritodrine was injected as an intravenous bolus into the mother. Maternal and fetal blood samples, amniotic fluid, and maternal urine were collected at time intervals. Samples were analyzed by a combination of high-pressure liquid chromatography and radiochromatography. Conjugated metabolites were recovered and characterized by cleavage studies with use of beta-glucuronidase and sulfatase. The distribution half-life of ritodrine in the mother was 6 minutes and the elimination half-life was 61 minutes. Metabolites were found in both fetal serum and amniotic fluid. The concentrations of ritodrine and its metabolites in fetal serum were at or above the concentrations in maternal serum at 2 hours after maternal intravenous injection. The principal metabolite identified was the sulfate conjugate. The fetus appears to accumulate metabolites. These data indicate that ritodrine crosses the placenta and, in the baboon, achieves levels in the fetus equal to or higher than those in the mother.     

Changes in thyroid status in pregnant women treated with ritodrine

In a clinical study of 17 pregnant women treated with ritodrine, a beta 2-sympathomimetic agent used for tocolysis, thyroid hormone status was assessed longitudinally. This was done in order to verify the hypothesis that an increase in T3 levels could result from adrenergic stimulation, since propranolol, a beta blocking agent, has proved to decrease T3 levels in man. Indeed, a statistically significant increase in T3 serum concentration and in T3/T4 ratio was found on the second day after the start of treatment with ritodrine (p less than 0.02 and less than 0.01 respectively). After discontinuation of treatment a decrease in T3 serum levels, compared to both treatment and pretreatment levels, was observed. The free T4 concentration showed a significant drop after the first week of treatment (p less than 0.01), but no changes were found in T4 and TSH levels. It was concluded that the beta 2-mimetic-mediated changes in thyroid status provide one more reason for restriction of the use of beta-mimetic drugs in hyperthyroidic patients and might offer an additional explanation for the undesirable chronotropic cardiac side-effects of the therapy.     

Combined maternal and congenital myotonic dystrophy managed by a multidisciplinary team

Myotonic dystrophy is a rare autosomal dominant degenerative neuromuscular and neuroendocrine disease. Pregnancy can aggravate the maternal disease. Obstetrical complications include stillbirth, premature labor, polyhydramnion, abnormal presentation, prolonged labor, increased operative delivery, postpartum hemorrhages and anesthetic accidents. If the fetus is affected severe neonatal morbidity and mortality with arthrogryposis and mental retardation is common. We present a case where the family chose continuation of pregnancy with a known diagnosis of maternal and severe fetal myotonic dystrophy. A multidisciplinary team was used in the management of pregnancy and counseling the patient.     

Nifedipine serum levels in pregnant women undergoing tocolysis with nifedipine.

The objective of our cross-sectional, observational study was to investigate nifedipine serum levels in pregnant women undergoing tocolysis. A total of 24 pregnant women, 22-34 weeks' gestation, who were administered nifedipine for treatment of pre-term labour, were enrolled in the study. Blood samples were taken 12 h after the oral application of 60 mg nifedipine in 'continuous release' form (Adalat CR 60). Nifedipine serum levels were measured with liquid chromatography. Nifedipine serum levels spread between 6 and 101 ng/ml (17-292 nmol/l). There was no correlation between nifedipine levels and body mass index (BMI), or between nifedipine levels and gestational age. During nifedipine tocolysis, 11 of 24 patients (45.8%) had mild side-effects, mostly headache. The side-effects were not dose-related. Despite the standardised dosage and standardised blood sampling nifedipine serum levels spread in a wide range. There is no need to adjust the dose of nifedipine to BMI or to gestational age.     

Rhabdomyolysis associated with Streptococcus pneumoniae bacteremia in a splenectomized patient.

Invasive infection due to Streptococcus pneumoniae associated with rhabdomyolysis is rare. We report the case of a 31-year-old splenectomized man with pneumococcal bacteremia and paranasal sinusitis who presented with flu-like symptoms preceding a fulminant course of sepsis and rhabdomyolysis with acute renal failure and elevated creatinine phosphokinase. Although the possible mechanisms of rhabodomyolysis associated with pneumococcal infection remain unclear, this report may serve to alert clinicians of the need to prevent fulminant pneumococcal infection by vaccination and treatment with antibiotic prophylaxis in splenectomized patients.     

Agranulocytosis associated with intravenous ritodrine hydrochloride therapy: two case reports by different mechanisms

Ritodrine hydrochloride has been widely used for tocolysis, although serious side-effects have been reported. We report two cases of agranulocytosis induced by ritodrine hydrochloride, which probably occurred by different mechanisms. Two patients were hospitalized because of preterm labor and were given intravenous ritodrine hydrochloride. The nadir of neutrocytes was 199/mm(3) and 13/mm(3) in the two cases, respectively. The total dose of ritodrine hydrochloride was calculated to be 7800 mg for 26 days and 2500 mg for 22 days, respectively. The total doses were heavier and administration duration was longer in Case 1, which suggested a toxic mechanism of agranulocytosis, while in Case 2, they were smaller and shorter, suggesting an immunological mechanism. For patients receiving ritodrine hydrochloride, the white blood cell count should be checked frequently regardless of the duration of therapy and a drug lymphocyte stimulation test should be performed.     

Ovarian reserve and PGD treatment outcome in women with myotonic dystrophy

Myotonic dystrophy (DM) is the most common form of muscular dystrophy in adults. There are conflicting reports about its effect on female fertility. This study investigated ovarian reserve and IVF–preimplantation genetic diagnosis (PGD) outcome in women with DM1. A total of 21 women undergoing PGD for DM1 were compared with 21 age- and body mass index-matched women undergoing PGD for other diseases. Ovarian reserve markers, response to stimulation, embryo quality and clinical pregnancy and live birth rates were compared. Day-3 FSH concentration was higher, while anti-Müllerian hormone concentration and antral follicle count were lower in the DM1 group (median, range: 6.9 (1.8–11.3) versus 5.7 (1.5–10.7) IU/l; 0.9 (0.17–5.96) versus 2.68 (0.5–9.1) ng/ml; and 13 (0–63) versus 23 (8–40) follicles, respectively, all P < 0.05). Total FSH dose was higher (5200 versus 2250 IU, P = 0.004), while the numbers of oocytes retrieved (10 versus 16, P < 0.04) and metaphase-II oocytes (9 versus 12, P < 0.03) were lower in the DM1 group. The number of cycles with top-quality embryos and the clinical pregnancy rate were lower in the DM1 group. In conclusion, there is evidence of diminished ovarian reserve and less favourable IVF–PGD outcome in women with DM1.Myotonic Dystrophy (DM) is the most common form of muscular dystrophy in adults. There is evidence of subfertility in males affected with the disease but conflicting reports about the effect of the disease on female fertility. The aim of our study was to investigate ovarian reserve and IVF–PGD results in women with DM. Twenty-one women undergoing preimplantation genetic diagnosis (PGD) treatment for DM were compared to 21 age- and BMI matched women undergoing PGD treatment for other diseases. The two groups were compared for antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) levels (the best known markers of ovarian reserve and fertility potential), ovarian response, embryo quality and pregnancy and live birth rates. AFC and the AMH levels were statistically significant lower in the DM group. Total medication dose needed for ovarian stimulation was higher, the number of oocytes and mature oocytes retrieved, and the number of cycles with top quality embryos were lower in the DM group compared to the controls. In conclusion, there is evidence of diminished ovarian reserve, and less favorable IVF-PGD outcome in women with DM. Therefore, we recommend advising these women about the possibility of early decreasing ovarian function in order to prevent any delay in reproductive planning.     

Torsion of a non-gravid leiomyomatous uterus in a patient with myotonic dystrophy complaining of acute urinary retention: anaesthetic management for total abdominal hysterectomy

Torsion of a pregnant uterus is rare, but torsion of a non-pregnant uterus is extremely rare. Abdominal pain is the major symptom. Other symptoms include vaginal bleeding, urinary tract symptoms and gastro-intestinal manifestations. We present a case of a 37-year-old white nullipara who presented at the emergency room with acute urinary retention. Medical history revealed that the patient carried the disease of myotonic dystrophy, which was diagnosed two years before. Physical examination revealed a tender, distended bladder, which was easily catheterized, draining 900 ml of clear urine. The abdomen was soft with no muscle guarding or rebound tenderness. A palpable large dense mass occupying the cul-de-sac was found during bimanual examination. Abdominal ultrasound examination revealed a large intramural leiomyoma approximately 10 cm in diameter, in the posterior wall of the uterus, which repelled the bladder. In neurological examination the muscular tone and reflexes were reduced in the lower extremities. Myotonic phenomenon was not found. The patient was thought to suffer from myotonic dystrophy and therefore the possibilities for pulmonary and cardiac complications or malignant hyperthermia had to be kept in mind during the anaesthetic management. The patient underwent an exploratory laparotomy and the uterus was found to have undergone a 60 degrees rotation along the corpus and the cervix uteri transition line. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was perfomed. The intra- and postoperative course of the patient was uneventful. In conclusion, in this patient the uterine pathology (large leiomyoma) in combination with the disease of myotonic dystrophy seemed to be the predisposing factors for the torsion of the non-pregnant uterus. Also, the anaesthetic implications for total abdominal hysterectomy in myotonic dystrophy are discussed and the international literature is reviewed.     

Oligohydramnios in a pregnant woman with Cushing's syndrome caused by an adrenocortical adenoma

A 28-year-old primigravida with severe oligohydramnios and pre-eclamptic symptoms was found to have Cushing's syndrome caused by an adrenocortical tumor. After meternal therapy the amniotic volume normalised, but the fetus succumbed. As clinical features of pre-eclampsia and Cushing's syndrome may overlap, diagnosis can be delayed or even missed.