Electrocardiographic findings during extended clinical trials of fluvoxamine in depression: one years experience.

INTRODUCTION: Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), is used to treat depression. No significant effect on the electrocardiogram (ECG) has been reported during short-term controlled studies of SSRI's. We report a long-term (1 year) multi-center, double-blind controlled study of the ECG during treatment of depression with fluvoxamine (FX), active control medication (TCA), and placebo (PLA). METHOD: Initially ECGs were obtained from 1840 physically healthy, depressed outpatients who were treated with FX, TCA, or PLA for 6 weeks. A subset of these patients continued treatment for up to one year. Complete sets of ECGs were obtained from 462 of these patients. Patients whose depression was substantially improved in the initial 6-week study ("responder") received the same medication. Non-responders received a blinded active medication. Pre-treatment, intra-study, and past-treatment ECGs were recorded according to protocol. One blinded electrocardiographer measured and analyzed all ECG data. The effects of each medication upon the ECG were measured and compared. RESULTS: Of the 462 patients, 311 used FX, 100 used TCA and 51 used PLA. Analyses of ECG data for each treatment focused on changes in ECG measurements; % of normal ECGs, and % of individual ECG findings. The ECG changes during FX treatment were less than or not significantly different from the ECG changes with PLA treatment. The changes with TCA were as expected. CONCLUSIONS: Fluvoxamine treatment of depression for one year was not associated with any significant effect on the ECG.

Continuous intrapartum measurement of tissue pH of the human fetus using newly developed techniques.

Using a fiberoptic probe with a dye indicator, pH was studied in a group of 124 fetuses. Acidotic tissue pH was found to be a far more powerful indicator of fetal, neonatal and maternal problems than acidotic capillary blood pH. The tissue pH related more consistently to obstetric problems throughout labor. A comparison was made of the reliability of fetal acidotic tissue pH and acidotic capillary blood pH data in the identification and prediction of obstetric problems.

Continuous tissue pH monitoring in the term fetus.

Since Saling's work in 1961, many investigators have attempted to perfect methods to detect fetal acidosis during labor. A system for continuous tissue pH monitoring of the fetus is evaluated in this study of 59 patients. There was poor correlation of tissue pH values and capillary scalp pH values in 19 cases (r = 0.487), and no significant correlation of tissue pH values to the outcome measurements of Apgar scores and cord gas levels. The benefits realized were those of monitoring the trend of tissue pH over time. We believe that a continuous pH monitoring system offers several advantages over intermittent fetal scalp sampling. Further refinement of the technology employed may offer such a system in the future.

Observations on perinatal heart rate monitoring. II. Quantitative unreliability of Doppler fetal heart rate variability.

Fifty-three fetal heart rate (FHR) tracings obtained by direct ECG monitoring during labor and 24 simultaneous external Doppler FHR tracings were analyzed for the quantitative assessment of baseline FHR variability. The beat-to-beat difference in FHR subsumed by 90% of all beat-to-beat changes within a tracing was taken as the index of variability of that tracing. This index correlated well with the visual assessment of variability for both internal ECG records (Spearman rank correlation coefficient, rs, = 0.71) and external Doppler records (rs = 0.78). However, there was no correlation between the variability index of the Doppler FHR records and that of simultaneous ECG FHR records (r = 0.11, p greater than 0.6). This finding casts doubt on the use of the presence of "normal" FHR variability as a sign of fetal well-being during antepartum FHR monitoring with current Doppler equipment.

Microprocessor-controlled doppler. A new fetal heart rate monitoring technique.

A new Doppler fetal heart rate (FHR) monitoring system using microprocessor-controlled ranged directional Doppler (RDD) was developed. The instrumentation was evaluated for accuracy and reproducibility of results by computer measurement and statistical analysis of the difference between FHR simultaneously obtained from Doppler and from fetal scalp electrocardiography (ECG) in 20 high-risk patients during labor. During 90% to 93.5% of the monitoring time, Doppler-derived FHR approximated ECG-FHR to within 5 beats per minute (BPM). The FHR records from this monitoring system can provide accurate and reliable external FHR information that may approximate the internal ECG-FHR record to such a degree that the practitioner is offered a reliable, noninvasive alternative to internal fetal monitoring.

Automatic detection of fetal movement by Doppler ultrasound during non-stress testing.

A new external fetal monitor, using a defocused, wide-area ultrasound transducer has been devised in order to obtain a more accurate representation of fetal movement during antepartum non-stress testing. The fetal activity Doppler signal is easily distinguished from the fetal heart Doppler and provides an automatic record of fetal movement which is objective and reproducible. In several clinical tests, this new monitor was found to be more sensitive and reliable than either reports of fetal movement from the mother or from a physician palpating the abdomen. This method of automatic detection of fetal activity can improve the accuracy of the non-stress test by providing an additional objective criteria.

The process of product selection in the medical instrument market.

Medical instrumentation is supplied by commercial organizations. Because the costs and risks of bringing new or advanced products to the market are high, the selection and evaluation process is critical. Moreover, the peculiarities of the medical instrumentation market add extra costs and risks. Major factors to be considered include the presence of a need, market acceptance, financial and technical viability, development time, internal resources, and the effect of FDA regulations. During the 5 to 7 years required to develop a new product, the difficulty of overcoming problems and the state of the market must be continually monitored. FDA documentation may necessitate 2 more years of effort. Market introduction includes proper market education, an appropriate plan of action, and constant monitoring of market reaction. Despite all these precautions, 70% of new products do not reach the market or do not survive in the market.

A study of the pH monitor in cats.

A study of the accuracy of the tpH electrode was performed in 10 cats. Hypoxia and acidosis were produced by ventilatory means and bicarbonate infusions were used to elevate the pH . Tissue pH correlated well with arterial (r = 0.9) within the physiological rates of change of pH. Prolonged tissue acidosis lead to eventual death. The correct and stable mechanical fixation of the pH electrode is a critical factor in assuring accurate results. The ROCHE tpH electrode accurately reflects arterial pH, and a correlation coefficient of at least 0.85 should be attainable in the human fetus.

New instrument developments for fetal pH monitoring.

Recent technical improvements in the ROCHE fetal pH monitor have simplified its use and increased the proportion of useful and accurate recordings. These improvements include electronic changes to reduce static electricity, a new spiral electrode which stabilizes the pH electrode in the fetal scalp, improved incision tools, simplified applicator tools, and a total system for reducing pH electrode handling during calibration.

Multicenter clinical trials of fetal pH monitoring in the U.S.A.

A multicenter collaborative study of the safety and clinical efficacy of the ROCHE fetal pH monitor has been started. A common protocol and reporting forms are used. As of April, 1978, 115 case reports have been received describing results with the latest hardware. The tissue pH monitor can be relied upon to monitor pH if the values are in the normal range. Comparison of tissue pH (tpH) with 146 capillary pH samples revealed 98% accuracy of tpH in classifying normal (greater than or equal to 7.20), but false tpH acidosis occurred in 6% of normals. Therefore, acidotic tpH values must be verified. Although six infants had some degree of trauma (small lacerations), there were no serious or permanent injuries.

Evaluation of continuous monitoring of tissue pH in cats.

An improved continuous tissue pH monitoring system, designed for human subcutaneous fetal scalp tissue, was evaluated in 10 cats for total of 60 hours. Respiratory acidosis was induced with and without hypoxia to model the pathology of human clinical fetal distress. Arterial and venous pH were sampled every 15 minutes and the values were compared to those from the pH monitor system. The values paralleled arterial and venous blood pH, with correlation coefficients up to 0.98 under various pathologic acidotic conditions.

Microfilm storage of fetal monitoring records: a practical solution.

Microfilming of fetal monitoring records has, at our institution, been found to be a practical method for storage of recording papers from fetal monitoring. This system permits a reduction of the records by a factor of 20:1 and up to 7.64 hours of fetal monitroing records will fit into a 4 x 6 inch film jacket. This microfilm record can easily be placed into a patient's chart and can thus easily be retrieved.

Observations in perinatal heart rate monitoring. I. A quantitative method of describing baseline variability of the fetal heart rate.

Simultaneous magnetic tape recordings of fetal scalp ECG, maternal ECG and uterine contractions were obtained from 23 patients in active labor. Computer-derived distributions of beat-to-beat changes were used to develop a simple numerical and graphical description of the long and short-term variability patterns. The visually observed variability may be described by the R-R interval change (beat-to-beat change), which is greater than 90% of the total number of beat-to-beat changes. Thus, the 90th percentile of R-R interval changes quantitatively describes the baseline variability. The variability may be classified as fixed, minimal, moderate or marked, based on this simple calculation. Graphs of cumulative percentage of R-R interval changes provide additional visual information. The effects of meperidine HCl on the observed variability were easily detected and visualized by these methods.

Technical aspects of ranged directional doppler: a new doppler method of fetal heart rate monitoring.

A new technique for clarifying the fetal heart Doppler signal (Ranged Directional Doppler) for fetal heart rate (FHR) monitoring has been developed. Ranged Directional Doppler enhances the signals of interest and, in addition, permits a separation of the Doppler signals generated by fast-moving structures of the fetal heart either toward or away from the transducer. The separation of the Doppler signals provides increased clarity and reduced baseline clutter. These Doppler signals may approach the fetal scalp ECG in signal-to-noise ratio, and they may provide a signal that allows more accurate external monitoring of long-term and short-term variability patterns of the FHR.

Variable range directional doppler and abdominal ECG for FHR monitoring.

Antepartum nonstress fetal heart rate (FHR) monitoring may become a valuable screening tool for all pregnancies. Two methods proposed for an antepartum FHR monitor are examined: abdominal electrocardiogram (AECG) and variable range directional Doppler (RDD). A good quality (detailed, clearcut baseline) RDD FHR record was obtained in 74/75 (99%) examinations, and a good quality AECG record was obtained i31/75 (41%). Each patient was monitored in the supine, lateral and sitting positions. Considering all positions, 76% of the RDD records and 19% of the AECG records were good. The RDD system was efficacious for routine, clinical antepartum FHR monitoring, but the performance of the AECG was too limited for this purpose.