Customized spectral band analysis compared with conventional Fourier analysis of heart rate variability in neonates.

A customized filtering technique is introduced and compared with fast Fourier transformation (FFT) for analyzing heart rate variability (HRV) in neonates from short-term recordings. FFT is classically the most commonly used spectral technique to investigate cardiovascular fluctuations. FFT requires stability of the physiological signal within a 300 s time window that is usually analyzed in adults. Preterm infants, however, show characteristics of rapidly fluctuating heart rate and blood pressure due to an immature autonomic regulation, resulting in non-stationarity of these signals. Therefore neonatal studies use (half-overlapping or moving) windows of 64 s length within a recording time of 2-5 min. The proposed filtering technique performs a filtering operation in the frequency range of interest before calculating the spectrum, which allows it to perform an analysis of shorter periods of only 42 s. The frequency bands of interest are 0.04-0.15 Hz (low frequency, LF) and 0.4-1.5 Hz (high frequency, HF). Although conventional FFT analysis as well as the proposed alternative technique result in errors in the estimation of LF power, due to spectral leakage from the very low frequencies, FFT analysis is more sensitive to this effect. The response times show comparable behavior for both the techniques. Applying both the methods to heart rate data obtained from a neonate before and after atropine administration (inducing a wide range of HRV), shows a very significant correlation between the two methods in estimating LF and HF power. We conclude that a customized filtering technique might be beneficial for analyzing HRV in neonates because it reduces the necessary time window for signal stability.

Educational simulation of the electroencephalogram (EEG).

We describe a model for simulating a spontaneous electroencephalogram (EEG) and for simulating the effects of anesthesia on the EEG, to allow anesthesiologists and EEG technicians to learn and practice intraoperative EEG monitoring. For this purpose, we developed a linear model to manipulate the amplitude of the activity in each of the traditional EEG frequency bands. Burst suppression patterns are simulated by manipulating an overall gain. To demonstrate the model feasibility, model parameters for thiopental and isoflurane were estimated guided by published data on the EEG effects of these anesthetic drugs. Using these estimates, EEG time signals were simulated for isoflurane at various partial pressures, and for bolus intravenous doses of thiopental. Comparison with actual recorded EEG signals showed that the changes produced by isoflurane and thiopental in the simulated signals are very similar to the changes in the actual signals, which was confirmed by two clinicians with experience and routine practice in intraoperative EEG monitoring.

Arterial stiffness as underlying mechanism of disagreement between an oscillometric blood pressure monitor and a sphygmomanometer.

Oscillometric blood pressure devices tend to overestimate systolic blood pressure and underestimate diastolic blood pressure compared with sphygmomanometers. Recent studies indicate that discrepancies in performance between these devices may differ between healthy and diabetic subjects. Arterial stiffness in diabetics could be the underlying factor explaining these differences. We studied differences between a Dinamap oscillometric blood pressure monitor and a random-zero sphygmomanometer in relation to arterial stiffness in 1808 healthy elderly subjects. The study was conducted within the Rotterdam Study, a population-based cohort study of subjects aged 55 years and older. Systolic and diastolic blood pressure differences between a Dinamap and a random-zero sphygmomanometer were related to arterial stiffness, as measured by carotid-femoral pulse wave velocity. Increased arterial stiffness was associated with higher systolic and diastolic blood pressure readings by the Dinamap compared with the random-zero sphygmomanometer, independent of age, gender, and average mean blood pressure level of both devices. The beta-coefficient (95% CI) was 0.25 (0.00 to 0.50) mm Hg/(m/s) for the systolic blood pressure difference and 0.35 (0.20 to 0.50) mm Hg/(m/s) for the diastolic blood pressure difference. The results indicate that a Dinamap oscillometric blood pressure device, in comparison to a random-zero sphygmomanometer, overestimates systolic and diastolic blood pressure readings in subjects with stiff arteries.

Event-related potential measures of information processing during general anesthesia.

To investigate the incidence and manner of auditory information processing during a state of presumed unconsciousness event-related brain potentials (ERPs) were studied in 41 patients undergoing cardiac surgery with propofol/alfentanil anesthesia. The ERPs were recorded during auditory oddball tasks administered before and within several periods of the operation. Mean nasopharyngeal temperature and anesthetic concentrations were determined for each intraoperative ERP recording epoch. During anesthesia ERP waves could still be observed up to 500 ms after stimulus onset indicating that auditory information processing was not suppressed completely by the administered anesthetic agents. Relative to the preoperative recordings, the P1-N1-P2 complex was delayed and more positive going during anesthesia. Comparable changes in ERP morphology have been observed during Stage II-IV sleep, suggesting parallels in the mechanisms underlying early auditory processing in both states of reduced arousal level, possibly related to a selective reduction of a non-specific activity. N1 and P2 peak amplitudes were found to be larger for the deviant tones compared to the standard tones. These amplitude differences most likely reflect automatic detection of stimulus deviance, although it cannot be excluded entirely that they were due to differences in refractoriness. Anesthetic concentrations and nasopharyngeal temperature were found to be of minor significance for ERP control. It is suggested that ERPs could serve as intraoperative reference measures, providing the earliest evidence for auditory processing. This characteristic is important for validation of signals and techniques that are proposed to improve conventional monitoring of anesthesia with respect to detecting unintended awareness.

Midlatency auditory evoked potentials as indicators of perceptual processing during general anaesthesia.

We tested the hypothesis that midlatency auditory evoked potentials (MLAEP) can predict the occurrence of long latency AEP components (LLAEP), which are taken as evidence for perceptual processing. Forty-one patients undergoing cardiac surgery were anaesthetized with propofol and alfentanil. During several periods of surgery we recorded LLAEP. Peak-to-peak amplitude measures were used to determine if a particular LLAEP recording trace contained a recognizable waveform. Both before and after each LLAEP recording epoch, MLAEP and the spontaneous electroencephalogram (EEG) were recorded. Peak latencies and amplitudes of brainstem peak V and midlatency peaks Na, Pa, Nb, Pb and Nc, characteristic frequencies from the spontaneous EEG, mean arterial pressure (MAP) and nasopharyngeal temperature (7) were compared between recording epochs with and without clear LLAEP waveforms. These variables were also used in a discriminant analysis to predict the occurrence of an LLAEP waveform. Pa and Nb latencies were significantly shorter both before and after recording epochs in which an LLAEP waveform occurred, compared with epochs in which no LLAEP waveform occurred. Using a combination of up to six EEG, MLAEP, MAP and T measures, it was possible to predict the occurrence or absence of an LLAEP waveform with a sensitivity of 89% and specificity of 86%. We conclude that MLAEP components provide information on the possibility of perceptual processing during general anaesthesia, and thus may be relevant for monitoring depth of anaesthesia.

Dehydroepiandrosterone reduces plasma plasminogen activator inhibitor type 1 and tissue plasminogen activator antigen in men.

Dehydroepiandrosterone (DHEA) may help prevent heart disease in men. To test the hypothesis that DHEA might exert its effects by enhancing endogenous fibrinolytic potential, a double-blind, placebo-controlled study was conducted that assessed the effects of DHEA administration on plasma plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (tPA) antigen. Eighteen men received 50 mg DHEA orally and 16 men received a placebo capsule thrice daily for 12 days. Serum DHEA-sulfate and plasma PAI-1 and tPA antigen were measured before and after treatment. In the DHEA group, serum DHEA-sulfate (from 7.5 +/- 1.2 micromol/L to 20.2 +/- 1.5 micromol/L (P < 0.0001), androstenedione (from 2.6 +/- 0.2 nmol/L to 4.0 +/- 0.4 nmol/L; P < 0.005) and estrone (from 172 +/- 21 pmol/L to 352 +/- 28 pmol/L; P < 0.005) increased, whereas plasma PAI-1 (from 55.4 +/- 3.8 ng/mL to 38.6 +/- 3.3 ng/mL; P < 0.0001) and tPA antigen (from 8.1 +/- 1.9 ng/mL to 5.4 +/- 1.3 ng/mL; P < 0.0005) decreased. In the placebo group, serum DHEA-sulfate declined slightly from 8.0 +/- 3.3 micromol/L to 7.3 +/- 3.4 micromol/L (P < 0.05), but no other measured steroid changed. Plasma PAI-1 and tPA antigen did not change in the placebo group. These findings suggest that DHEA administration reduces plasma PAI-1 and tPA antigen concentrations in men.

Haemodynamic responses to incision and sternotomy in relation to the auditory evoked potential and spontaneous EEG.

We investigated the effect of incision and sternotomy on the auditory evoked potential (AEP) and EEG, to try to predict a haemodynamic response to incision or sternotomy using the AEP and EEG in 41 patients undergoing cardiac surgery during propofol and alfentanil anaesthesia. The AEP and EEG were recorded before incision, between incision and sternotomy, and after sternotomy. Peak latencies and amplitudes of AEP peaks V, Na, Pa, Nb, Pb and Nc were determined. From the EEG the median, spectral edge and peak power frequencies, and percentages of delta, theta, alpha and beta power were calculated. Each patient was classified as responsive, equivocally responsive or unresponsive to incision or sternotomy based on increase in arterial pressure and heart rate on incision and sternotomy. Before incision, Nb and Pb latency and propofol concentration were higher for unresponsive patients but heart rate and median frequency before incision were lower. After sternotomy, Pa and Nb amplitude, peak power frequency and percentage alpha power were higher, and percentage theta power lower for responsive patients. Pa latency was higher after sternotomy for unresponsive patients. Using a combination of heart rate, arterial pressures and features derived from the AEP (all recorded before incision), the occurrence of a response to incision could be predicted in individual patients with a sensitivity of 85%, positive predictive accuracy of 63% and total accuracy of 72%. We conclude that AEP are more sensitive to pain stimuli than spectral features of the spontaneous EEG. In addition, the AEP may help in predicting inadequate anaesthesia.

Disparate effects of weight reduction by diet on serum dehydroepiandrosterone-sulfate levels in obese men and women.

To assess the effect of weight reduction on serum dehydroepiandrosterone (DHEA)-sulfate, insulin, and glucose, these parameters were assessed in 18 men and 29 women before and after weight loss achieved by a 2-month 1000-1400 kcal diet. Men and women did not differ at baseline with respect to age, body mass index (BMI), or serum insulin and glucose, but serum DHEA-sulfate was almost 2-fold higher in women than men (5.4 +/- 0.5 vs. 2.8 +/- 0.2 mumol/L; P < 0.001). During the diet, men and women experienced similar reductions in BMI of 3.5 kg/m2 and 3.2 kg/m2, respectively. Fasting serum insulin fell by 38% in men and 33% in women, and did not differ between sexes at the diet's end (135 +/- 7 vs. 156 +/- 8 pmol/L; P = NS). Serum glucose fell slightly in both men and women, but did not differ between sexes. Weight loss in men was associated with a 125% rise in serum DHEA-sulfate from 2.8 +/- 0.2 to 6.3 +/- 0.3 mumol/L (P < 0.0001). In contrast, serum DHEA-sulfate did not change with weight loss in women (P = 0.35). Serum DHEA-sulfate at the end of the diet did not differ between men and women (6.3 +/- 0.3 vs. 5.2 +/- 0.5 mumol/L; P = 0.10). Hence, dietary weight loss accompanied by equivalent reductions in body mass index and serum insulin between sexes was associated with a marked rise in serum DHEA-sulfate in men, whereas in women serum DHEA-sulfate did not change. Although speculative, these findings are consistent with the idea that insulin acts in a sex-specific fashion to reduce circulating DHEA-sulfate in men only.

Clinical evaluation of a method for automatic detection and removal of artifacts in auditory evoked potential monitoring.

OBJECTIVE: The objective of our study was to evaluate the method for detection and removal of artifacts in evoked potential monitoring described earlier by Cluitmans and colleagues in a clinical setting. METHODS: The method for detection and removal of artifacts by Cluitmans and colleagues is based on the assumption that a sweep of the recorded electroencephalogram (EEG) signal contains artifacts if one or more variables derived from the signal deviates strongly from the normal range of values. Once these normal ranges are defined, all future EEG recordings that are recorded under comparable circumstances can be automatically evaluated for artifacts by tracking when one or more signal variables falls outside the normal range. To assess the performance of this method in a clinical setting, recordings from a learning set were visually evaluated for artifacts. From the empirical distribution functions of the signal variables, the thresholds for automatic detection of artifacts were determined. The auditory evoked potential (AEP) waveforms resulting after automatic screening were compared with the waveforms obtained after visual evaluation of the raw signal combined with manual exclusion of signal periods containing artifacts. RESULTS: The quality of the resulting waveform was improved by our method of automatic detection and removal of artifacts in 97% of partly contaminated recordings. In only 2% of the recordings, automatic screening slightly degraded the resulting waveform. CONCLUSIONS: We conclude that the described method of automatic detection and removal of artifacts in AEP recordings effectively improves the quality of the resulting AEP waveform, without excessive rejection of artifact-free signal periods. The signal variables used in this method seem appropriate for distinguishing artifact-free signal periods from periods containing artifacts for the types of artifact that were studied.

Information processing during cardiac surgery: an event related potential study.

The aim of this study was to investigate whether information processing persists during general anesthesia, and if so, to determine the relationship between the degree of cognitive processing measured during anesthesia and the presence or absence of intraoperative memories measured after anesthesia. Subjects were 12 patients, undergoing cardiac surgery with propofol/alfentanil anesthesia. During several periods of the operation, event related potentials (ERPs) to frequent and infrequent tones of different pitch were analyzed. After the operation, a word recognition task with ERP recording was administered to determine whether intraoperatively presented words would elicit a (covert) recognition reaction in the brain. ERP wave forms could be obtained during the intraoperative recording periods but differed substantially from those in the awake state. The presence of ERP components up to 500 msec after stimulus presentation suggests that auditory information processing continued during anesthesia up to a certain level of cognition. Intraoperative ERPs to frequent and infrequent tones were not different from each other implying that differences in pitch could not be detected. The postoperative results demonstrated evidence for intraoperative memories in 3 patients. For 2 of these 3 patients, low propofol levels as well as reliable ERPs with large amplitudes were found close to the moment of information presentation. The results emphasize the importance of combining intra- and postoperative measurements and suggest that late ERP components might be used as indicators of an increased risk of auditory perception.

Effects of insulin reduction with benfluorex on serum dehydroepiandrosterone (DHEA), DHEA sulfate, and blood pressure in hypertensive middle-aged and elderly men.

To determine whether a reduction in insulinemia would be associated with a rise in serum dehydroepiandrosterone (DHEA) sulfate in insulin-resistant men, 29 middle-aged (30-59 yr old) and 28 elderly (60-80 yr old) hypertensive men were enrolled into a single blind, placebo-controlled study, in which benfluorex was administered to improve insulin sensitivity and reduce circulating insulin. Men in each age group received either benfluorex (150 mg) or placebo three times daily for 6 weeks, and fasting serum insulin, glucose, DHEA, DHEA sulfate, and cortisol were determined before and after treatment. Glucose tolerance was also assessed by an oral glucose tolerance test. Benfluorex treatment lowered diastolic and systolic blood pressures and improved glucose tolerance in both age groups. In middle-aged men, benfluorex (n = 12) reduced both the area under the curve for glucose (AUCGLUCOSE; from 977 +/- 27 to 814 +/- 27 mmol/L.min; P = 0.0001) and the AUCINSULIN (from 78.1 +/- 7.9 to 44.5 +/- 5.7 nmol/L.min; P < 0.0001) during the oral glucose tolerance test. In elderly men, benfluorex (n = 15) also reduced both the AUCGLUCOSE (from 1100 +/- 60 to 864 +/- 26 mmol/L.min; P < 0.0001) and the AUCINSULIN (from 88.9 +/- 5.6 to 44.8 +/- 5.8 nmol/L.min; P < 0.0001). Concurrent with the reduction in insulinemia, benfluorex treatment was associated with rises in both serum DHEA sulfate and unconjugated DHEA. In middle-aged men, serum DHEA sulfate and DHEA rose from 6.80 +/- 0.75 to 10.52 +/- 1.02 mumol/L (P < 0.015) and from 13.69 +/- 1.95 to 22.78 +/- 2.90 nmol/L (P < 0.03), respectively. In elderly men, serum DHEA sulfate and DHEA rose from 5.16 +/- 0.67 to 8.36 +/- 1.21 mumol/L (P < 0.015) and from 8.47 +/- 0.99 to 22.61 +/- 3.24 nmol/L (P < 0.0005), respectively. In neither middle-aged nor elderly men did serum cortisol change with benfluorex treatment. Neither glucose tolerance nor serum DHEA, DHEA sulfate, or cortisol levels changed in either middle-aged (n = 17) or elderly (n = 13) men treated with placebo. We conclude that benfluorex treatment lowers blood pressure, improves glucose tolerance, reduces the glucose-stimulated insulin response, and increases serum DHEA and DHEA sulfate in both middle-aged and elderly men.(ABSTRACT TRUNCATED AT 400 WORDS)

Disparate effects of insulin reduction with diltiazem on serum dehydroepiandrosterone sulfate levels in obese hypertensive men and women.

Evidence suggests that amelioration of hyperinsulinemic insulin resistance in men with calcium channel blockers of the dihydropyridine class is associated with a fall in serum insulin and a rise in serum dehydroepiandrosterone sulfate (DHEA-S) concentrations. The present study was conducted to determine whether 1) the nondihydropyridine calcium channel blocker diltiazem also reduces circulating insulin levels in humans, and 2) a reduction in circulating insulin with a calcium channel blocker is associated with a rise in serum DHEA-S concentrations in women as well as men. Ten obese hypertensive men and 13 obese hypertensive postmenopausal women were studied. Subjects were assessed at baseline and after the oral administration of diltiazem (60 mg, three times daily) for 18 days. Diltiazem treatment was associated with reductions in fasting serum insulin levels in both the men (from 91 +/- 14 to 56 +/- 12 pmol/L; P < 0.03) and women (from 92 +/- 20 to 48 +/- 9 pmol/L; P = 0.05). Serum glucose levels did not change in either group. In men, concurrent with the fall in serum insulin levels, serum DHEA-S levels rose from 4.05 +/- 1.06 to 6.91 +/- 1.32 mumol/L (P < 0.04), and serum DHEA levels rose from 14.4 +/- 3.0 to 24.3 +/- 4.6 nmol/L (P = 0.05) with diltiazem treatment, whereas serum cortisol did not change. In contrast, diltiazem administration in the women was not associated with any change in serum DHEA-S, DHEA, or cortisol levels. These observations suggest that the action of calcium channel blockers to lower fasting serum insulin levels is not specific for the dihydropyridine class and applies to both men and women. Furthermore, the finding of a sex-based disparity in DHEA-S and DHEA responses to insulin reduction suggests that the metabolism of these steroids may be regulated differently in men than in women.

Effects of a reduction in circulating insulin by metformin on serum dehydroepiandrosterone sulfate in nondiabetic men.

Evidence suggests that hyperinsulinemic insulin resistance may reduce serum levels of the adrenal steroid dehydroepiandrosterone (DHEA) sulfate in humans. This study was conducted to assess the influence of physiological concentrations of insulin on serum adrenal steroid levels by lowering circulating insulin in nondiabetic men through the administration of the biguanide metformin. A total of 28 nondiabetic men were studied. The study group consisted of 16 obese and hypertensive men, and the control group of 12 nonobese and normotensive men. The men were studied at baseline and after the oral administration of 500 mg metformin, 3 times daily, for 21 days. Metformin administration resulted in significant reductions in serum insulin levels and concurrent increases in serum DHEA sulfate levels in both groups of men. The mean fasting serum DHEA sulfate concentration rose by 48% in the obese hypertensive men (from 5.9 +/- 0.8 to 8.7 +/- 0.7 mumol/L; P < 0.02) and by 80% in the nonobese normotensive men (from 3.5 +/- 0.5 to 6.3 +/- 0.9 mumol/L; P < 0.05). When the results from both groups were combined, changes in serum DHEA sulfate levels (i.e. day 21 value minus day 0 value) correlated positively with baseline fasting serum insulin levels (r = 0.44; P = 0.02; n = 28). Moreover, changes in fasting serum DHEA sulfate levels correlated inversely with changes in fasting serum insulin levels (r = -0.38; P < 0.05; n = 28). These findings lend further credence to the idea that insulin acts as a physiological regulator of DHEA sulfate metabolism and lowers circulating DHEA sulfate concentrations in men.

The calcium channel blocker amlodipine raises serum dehydroepiandrosterone sulfate and androstenedione, but lowers serum cortisol, in insulin-resistant obese and hypertensive men.

To determine whether the calcium channel blocker amlodipine improves glucose tolerance and alters serum adrenal androgen and glucocorticoid levels in insulin-resistant men, 24 obese and hypertensive men were enrolled into a single blind, placebo-controlled study. An amlodipine group (n = 12) and a placebo group (n = 12) were studied before and after treatment with either amlodipine (5 mg) or placebo capsule twice daily for 7 days by determining serum insulin, glucose, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, and cortisol in the fasting state and during an oral glucose tolerance test. Amlodipine treatment 1) lowered fasting serum insulin (from 273 +/- 19 to 200 +/- 17 pmol/L; P < 0.0005) and glucose (from 5.4 +/- 0.1 to 5.1 +/- 0.1 mmol/L; P < 0.02), 2) reduced the area under the curve for glucose (from 1342 +/- 25 to 1198 +/- 23 mmol/L.min; P = 0.0001) and the area under the curve for insulin (from 155.5 +/- 7.8 to 103.9 +/- 4.3 nmol/L.min; P = 0.0001) during the oral glucose tolerance test, 3) increased fasting serum DHEA-S (from 5.19 +/- 0.37 to 7.95 +/- 0.58 mumol/L; P = 0.0001) and androstenedione (from 5.65 +/- 0.65 to 6.83 +/- 0.53 nmol/L; P < 0.01), and 4) decreased fasting serum cortisol (from 538 +/- 35 to 494 +/- 26 nmol/L; P < 0.05). Fasting serum androstenedione declined slightly in the placebo group (from 5.96 +/- 0.60 to 5.74 +/- 0.57 nmol/L; P < 0.005), but no change occurred in glucose tolerance, fasting serum DHEA-S, or cortisol. We conclude that amlodipine treatment improves glucose tolerance, reduces fasting and glucose-stimulated serum insulin levels, increases serum DHEA-S and androstenedione levels, and decreases circulating cortisol.

Effects of nitrendipine on glucose tolerance and serum insulin and dehydroepiandrosterone sulfate levels in insulin-resistant obese and hypertensive men.

To determine whether the calcium channel blocker nitrendipine improves glucose tolerance, lowers circulating insulin, and raises serum dehydroepiandrosterone sulfate (DHEA-S) levels in insulin-resistant men, a total of 15 obese and hypertensive men were enrolled in a single blind, placebo-controlled study. A nitrendipine group (n = 8) and a placebo group (n = 7) were studied before and after treatment with either nitrendipine (10 mg) or a placebo capsule, twice daily for 7 days, by determining serum insulin, glucose, and DHEA-S levels in the fasting state and during an oral glucose tolerance test. Nitrendipine treatment 1) lowered fasting serum insulin from 265 +/- 24 to 194 +/- 22 pmol/L (P < 0.01) without changing fasting serum glucose, 2) reduced both the area under the curve for glucose (from 1246 +/- 31 to 1091 +/- 26 mmol/L.min; P < 0.005) and the area under the curve for insulin (from 123.6 +/- 9.4 to 82.9 +/- 10.0 nmol/L.min; P < 0.015) during the oral glucose tolerance test, and 3) increased fasting serum DHEA-S by 63% from 4.21 +/- 0.17 to 6.84 +/- 0.21 mumol/L (P = 0.0001). No change was noted in the placebo group. We conclude that nitrendipine treatment is associated with improved glucose tolerance, reduced fasting and glucose-stimulated serum insulin levels, and increased circulating DHEA-S levels.