Electrocardiographic changes associated with β-blocker toxicity

Study objective: We sought to characterize the ECG changes associated with symptomatic β-blocker overdose. Methods: The study population consisted of a prospective cohort of patients reporting to 2 regional poison centers with β-blocker overdose. Each patient received an ECG on presentation and a structured follow-up. The inclusion criteria for symptomatic overdose included heart rate of less than 60 beats/min or systolic blood pressure of less than 90 mm Hg; symptoms consistent with decreased end-organ perfusion; therapeutic intervention with cardioactive medication; and corroboration by 2 of the authors that this was a clear-cut case of symptomatic β-blocker overdose with cardiovascular toxicity. Exclusion criteria included cardioactive coingestants, age younger than 6 years, and no available ECG. Results: Of 167 patients, 13 were determined to have symptomatic exposures. First-degree heart block (>200 ms) was the most common ECG finding (10/12) and also had the greatest likelihood ratio (5.31) when comparing those with symptomatic exposures with those with asymptomatic exposures. Comparing the asymptomatic with the symptomatic groups, the mean PR interval was 167 ms (95% confidence interval [CI] 162 to 171 ms) versus 216 ms (95% CI 193 to 238 ms), the mean QRS interval was 89 ms (95% CI 87 to 91 ms) versus 112 ms (95% CI 92 to 132 ms), the mean QTc interval was 422 ms (95% CI 417 to 428) versus 462 ms (95% CI 434 to 490 ms), and the mean heart rate was 72 beats/min (95% CI 69 to 74 beats/min) versus 66 beats/min (95% CI 59 to 73 beats/min). Two cases of symptomatic acebutolol exposure appeared unique by demonstrating disproportionate prolongation of the QTc interval, an RaVR height of 3 mm or greater, and associated ventricular tachydysrhythmia. Conclusion: The majority of clinically significant β-blocker intoxications demonstrate negative dromotropic effects on ECG. Several ECG differences in acebutolol intoxication might reflect unique pathophysiologic processes relative to other β-blockers. [Ann Emerg Med. 2002;40:603-610.]     

Hair cortisol in pregnancy interacts with maternal depressive symptoms to predict maternal disrupted interaction with her infant at 4 months

Disrupted maternal interaction in early infancy is associated with maladaptive child outcomes. Thus, identifying early risk factors for disrupted interaction is an important challenge. Research suggests that maternal depressive symptoms and maternal cortisol dysregulation are associated with disrupted maternal interaction, but both factors have rarely been considered together as independent or interactive predictors of disrupted interaction. In a sample of 51 women, hair cortisol concentrations (HCC) and depressive symptoms were assessed during pregnancy, and depressive symptoms were assessed again at 4-month postpartum. Maternal disrupted interaction was assessed during the Still-Face Paradigm at 4 months. Results indicated that HCC and depressive symptoms interacted to predict both maternal withdrawing and inappropriate/intrusive interaction. Withdrawing interaction was associated with high levels of HCC in pregnancy in the context of high depressive symptoms at 4 months; inappropriate/intrusive interaction was associated with high levels of HCC in the context of low depressive symptoms. Thus, high HCC potentiated both forms of disrupted interaction. Results raised questions about the meaning of very low reported depressive symptoms, and underscored the importance of chronic stress physiology and maternal depressed mood as risk factors for distinct forms of maternal disrupted interaction, both of which are deleterious for infant development.     

Cardiac sympathetic activation and parasympathetic withdrawal during psychosocial stress exposure in 6-month-old infants

Infant autonomic reactivity to stress is a potential predictor of later life health complications, but research has not sufficiently examined sympathetic activity, controlled for effects of physical activity and respiration, or studied associations among autonomic adjustments, cardiac activity, and affect in infants. We studied 278 infants during the repeated Still-Face Paradigm, a standardized stressor, while monitoring cardiac activity (ECG) and respiratory pattern (respiratory inductance plethysmography). Video ratings of physical activity and affect were also performed. Respiratory sinus arrhythmia (RSA) and T-wave amplitude (TWA) served as noninvasive indicators of cardiac parasympathetic and sympathetic activity, respectively. Responses were compared between infants who completed two still-face exposures and those who terminated after one exposure due to visible distress. Findings, controlled for physical activity, showed robust reductions in respiration-adjusted RSA and TWA, with more tonic attenuation of TWA. Infants completing only one still-face trial showed more pronounced autonomic changes and less recovery from stress. They also showed elevated minute ventilation, suggesting hyperventilation. Both reductions in adjusted RSA and TWA contributed equally to heart rate changes and were associated with higher negative and lower positive affect. These associations were more robust in the group of distressed infants unable to complete both still-face trials. Thus, cardiac sympathetic activation and parasympathetic withdrawal are part of the infant stress response, beyond associated physical activity and respiration changes. Their association with cardiac chronotropy and affect increases as infants' distress level increases. This excess reactivity to social stress should be examined as a predictor of future cardiovascular disease.     

Maternal sensitivity and infant autonomic and endocrine stress responses

Background

Early environmental exposures may help shape the development of the autonomic nervous system (ANS) and hypothalamic–pituitary–adrenal (HPA) axis, influencing vulnerability for health problems across the lifespan. Little is known about the role of maternal sensitivity in influencing the development of the ANS in early life.

Aims

To examine associations among maternal sensitivity and infant behavioral distress and ANS and HPA axis reactivity to the Repeated Still-Face Paradigm (SFP-R), a dyadic stress task.

Study design

Observational repeated measures study.

Subjects

Thirty-five urban, sociodemographically diverse mothers and their 6-month-old infants.

Outcome measures

Changes in infant affective distress, heart rate, respiratory sinus arrhythmia (RSA), and T-wave amplitude (TWA) across episodes of the SFP-R were assessed. A measure of cortisol output (area under the curve) in the hour following cessation of the SFP-R was also obtained.

Results

Greater maternal insensitivity was associated with greater infant sympathetic activation (TWA) during periods of stress and tended to be associated with greater cortisol output following the SFP-R. There was also evidence for greater affective distress and less parasympathetic activation (RSA) during the SFP-R among infants of predominantly insensitive mothers.

Conclusions

Caregiving quality in early life may influence the responsiveness of the sympathetic and parasympathetic branches of the ANS as well as the HPA axis. Consideration of the ANS and HPA axis systems together provides a fuller representation of adaptive versus maladaptive stress responses. The findings highlight the importance of supporting high quality caregiving in the early years of life, which is likely to promote later health.     

Research on control of craniofacial morphogenesis: an NIDR State-of-the-Art Workshop.

To assess the wide clinical ramifications of control of craniofacial morphogenesis, a State-of-the-Art Workshop was conducted by the National Institute of Dental Research at the initiative of Richard L. Christiansen, Chief of the Craniofacial Anomalies Program. In conjunction with the authors listed above, the format for the workshop was developed and participants were selected. The workshop was designed to provide an in-depth review of present knowledge and to identify future goals and directions for research on guiding, altering, and thus controlling growth and development of the cranofacial skeleton. The agenda for discussion ranged from molecular biology to clinical arts such as orthopedics and surgery. It was evident during the workshop that the mechanisms and procedures for controlling craniofacial morphogenesis must be derived from many biologic, physical, and clinical fields of knowledge. It is hoped that there will evolve an interdisciplinary clinical art which is aimed at preventing and correcting craniofacial deformities. Substantial biologic information has already been accumulated on the craniofacial skeleton. The clinical art of correcting malocclusion through mechanical forces is now applicable to the entire skull. The outstanding technical accomplishments of radical surgery in the correction of congenital craniofacial anomalies show that the needed surgical skills are now available. When these resources are combined, an area of knowledge and a clinical discipline which might be called "orthocephalics" is already identifiable. The workshop was held at the National Institutes of Health in Bethesda, Maryland, on Feb. 12 and 13, 1974. The ideas exchanged were integrated and summarized by the planning committee to produce this report.     

Effect of levofloxacin coadministration on the international normalized ratios during warfarin therapy

STUDY OBJECTIVE: To evaluate the effect of levofloxacin coadministration on the international normalized ratio (INR) in patients receiving warfarin therapy. DESIGN: Prospective analysis. SETTING: Outpatient clinic at a Veterans Affairs medical center. PATIENTS: Eighteen adult patients receiving warfarin. INTERVENTION: On the basis of clinical diagnosis and judgment, levofloxacin was prescribed to the 18 patients for treatment of various types of infection. The INR was measured before and at 2-8-day intervals after the coadministration of levofloxacin therapy, and once after completing therapy. Warfarin dosages were adjusted when necessary. MEASUREMENTS AND MAIN RESULTS: Warfarin dosages were changed in seven patients as a result of the first nontherapeutic INR values obtained after start of levofloxacin therapy. Owing to a concern regarding noncompliance and the adverse effect of bleeding, warfarin dosage was adjusted in one patient even though his first INR value was in the high end of the therapeutic range (2.98, therapeutic range 2-3). One patient withdrew from the study after the first INR measurement after levofloxacin coadministration. Because of a concern about the possible bleeding complication, warfarin dosage was also adjusted in this patient after obtaining his first INR value. Therefore, only the INR values obtained before and the first INR values obtained after levofloxacin administration were compared to evaluate the effect of levofloxacin on INR determination of warfarin therapy. The INR values obtained before levofloxacin administration did not differ significantly from the first INR values obtained after levofloxacin coadministration (mean +/- SD 2.61 +/- 0.44 vs 2.74 +/- 0.83, 95% confidence interval -0.449-0.196, p=0.419). CONCLUSION: The INR values measured before and after concomitant levofloxacin therapy were not significantly different. However, the ability to detect a significant difference may be affected by the small number of patients studied. Further studies with a larger sample are required to better determine the effect of levofloxacin coadministration on INR monitoring during warfarin therapy