Michael Mueck-Weymann

Short-term effects of intravenous benzodiazepines on autonomic neurocardiac regulation in humans: a comparison between midazolam, diazepam, and lorazepam.

ObjectivesTo evaluate the effects of intravenously applied diazepam, lorazepam, and midazolam on autonomic neurocardiac regulation assessed by standardized measurements of heart rate variability. DesignProspective, randomized clinical study. SettingUniversity teaching hospital. PatientsForty-five patients, who underwent a gastroscopy, were randomly assigned to intravenous premedication with midazolam (5 mg), diazepam (10 mg), or lorazepam (4 mg). Six subjects refused an injection and served as nonpremedicated controls. InterventionsSerial recordings of the 5-min resting heart rate variability were obtained before and 15 and 30 mins after premedication. Seven benzodiazepine-treated patients received intravenous flumazenil (0.5 mg). Measurements and Main ResultsThe average doses applied were 0.07 mg/kg for midazolam, 0.13 mg/kg for diazepam, and 0.06 mg/kg for lorazepam. Fifteen minutes after intravenous benzodiazepines were administered, we found an increase in resting heart rate and a reduction of vagal tone compared with baseline in all three benzodiazepine-treated subgroups. Multivariate analysis (covariate age) of the changes in heart rate variability indices over the experimental course revealed a significant reduction in absolute high-frequency power with midazolam or diazepam compared with nonpremedicated subjects. Moreover, midazolam-treated subjects showed a significantly larger reduction in relative high-frequency power not only compared with nontreated subjects, but also compared with lorazepam- or diazepam-treated subjects. Vagal tone remained reduced compared with baseline even 30 mins after benzodiazepine application, however, the resting heart rate decreased toward baseline levels. After flumazenil administration, there was a linear correlation between an increase in high-frequency power and a corresponding decrease in resting heart rate. ConclusionsBenzodiazepines can influence autonomic neurocardiac regulation in man, probably through their interaction with the &ggr;-aminobutyric acidA-receptor chloride ion channel complex. The pattern of findings suggests that intravenous midazolam, diazepam, and lorazepam influence human autonomic neurocardiac regulation in a biphasic way. First, they cause a reduction of central vagal tone, and second, they may decrease the cardiac pacemaker directly. Flumazenil completely abolished the autonomic neurocardiac regulation effects of benzodiazepines.

Comparison of heart rate variability and pulse rate variability detected with photoplethysmography

This study compares ear photoplethysmography (PPG) and electrocardiogram (ECG) in providing accurate heart beat intervals for use in calculations of heart rate variability (HRV, from ECG) or of pulse rate variability (PRV, from PPG) respectively. Simultaneous measurements were taken from 44 healthy subjects at rest during spontaneous breathing and during forced metronomic breathing (6/min). Under both conditions, highly significant (p > 0.001) correlations (1.0 > r > 0.97) were found between all evaluated common HRV and PRV parameters. However, under both conditions the PRV parameters were higher than HRV. In addition, we calculated the limits of agreement according to Bland and Altman between both techniques and found good agreement (< 10% difference) for heart rate and standard deviation of normal-to-normal intervals (SDNN), but only moderate (10-20%) or even insufficient (> 20%) agreement for other standard HRV and PRV parameters. Thus, PRV data seem to be acceptable for screening purposes but, at least at this state of knowledge, not for medical decision making. However, further studies are needed before more certain determination can be made.

The effects of sildenafil on heart rate variability in healthy subjects.

The effects of sildenafil on heart rate variability were investigated in 20 healthy male subjects aged 24 (21 to 32) years (median; range). Subjects orally received single 100-mg doses of sildenafil and placebo under randomized double-blind crossover conditions on 2 separate study days. Time domain measures of heart rate variability were assessed under conditions of relaxed rest, metronomic breathing (6 cycles per minute), and bicycle ergometry before administration of sildenafil and placebo as well as 60 minutes afterwards. Sildenafil did not alter heart rate nor heart rate variability to a significant extent (P > 0.05).

Detection of inspiratory-induced vasoconstrictive episodes using laser Doppler fluxmetry and photopletysmography

Laser Doppler fluxmetry (LDF) or photopletysmography (PPG) are frequently used as non-invasive tools for the detection of the so-called “inspiratory gasp response” (IGR), a vasoconstrictive episode provoked by a voluntary deep inspiration. According to our knowledge, a rigorous comparison of both methods has not been reported in the literature. Therefore, the aim of the study was to compare the detection of IGR with LDF and PPG. We investigated 14 young and healthy volunteers. A PPG and a LDF probe were applied to adjacent fingertips of the dominant hand (thumb/index finger). After baseline measurements the subjects were asked to perform a deep inspiration with time intervals of 90 sec., 60 sec., 30 sec., and 15 sec. We found that both methods are useful to detect individual IGR. However, overall correlation of IGR amplitude detected with LDF and PPG was poor (r=0.433). Surprisingly, there was a continuous increase of the correlation coefficient from the first (r=0.105) or second (r=0.184) IGR to the fifth (r=0.727) IGR. These results imply that experimental data obtained with PPG and LDF are not equivalent and therefore one has to be cautious regarding the comparison and interpretation of results obtained with these two different methods.