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Anesth Analg 2000;91:1188-1195
© 2000 International Anesthesia Research Society

CRITICAL CARE AND TRAUMA

Dynamic Cardiocirculatory Control During Propofol Anesthesia in Mechanically Ventilated Patients

Cornelius Keyl, MD*, Annette Schneider, MD*, Martin Dambacher, MD{ddagger}, Ulrike Wegenhorst, MD*, Matthias Ingenlath, MD*, Michael Gruber, PhD*, and Luciano Bernardi, MD{dagger}

*Department of Anesthesiology, University Medical Center, University of Regensburg, Germany; {dagger}Department of Internal Medicine, University of Pavia and Istituto di Ricovero e Cura a Carattere Scientifico S. Matteo, Pavia, Italy; and {ddagger}Fraunhofer IPM, Freiburg, Germany

Address correspondence and reprint requests to Cornelius Keyl, MD, Department of Anesthesiology, University Medical Center, 93042 Regensburg, Germany. Address e-mail to Keyl{at}rkananw1.ngate.uni-regensburg.de


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
We evaluated dynamic cardiovascular control by spectral analytical methods in 20 young adults anesthetized with propofol (2.5 mg/kg, followed by continuous infusion of 0.1 mg/kg/min) and in an awake control group during cyclic stimulation of the carotid baroreceptors via sinusoidal neck suction at 0.2 Hz (baroreflex response mediated mainly by vagal activity) and at 0.1 Hz (baroreflex response mediated by vagal and sympathetic activity). During anesthesia and mechanical ventilation at 0.25 Hz, major underdampened hemodynamic oscillations occurred at 0.055 ± 0.012 Hz. The response of RR intervals to baroreceptor stimulation at 0.2 Hz was markedly decreased during anesthesia (median of transfer function magnitude between neck suction and RR intervals 3% of the awake control). Blood pressure response to baroreceptor stimulation at 0.1 Hz was significantly decreased during anesthesia to 26% (systolic blood pressure), and 44% (diastolic blood pressure) of the awake control. There was a significant delay in baroreflex effector responses during anesthesia. Our results demonstrate a markedly depressed vagally mediated heart rate response and an impaired blood pressure response to cyclic baroreceptor stimulation during propofol anesthesia in mechanically ventilated patients. The disturbed baroreflex control is accompanied by an irregular dynamic behavior of cardiovascular regulation, indicating a decreased stability of the control system.

Implications: An irregular dynamic behavior of the cardiovascular control system, associated with an impaired baroreflex control of heart rate and blood pressure, can be observed during propofol anesthesia in mechanically ventilated subjects.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Hemodynamic side effects of anesthetic drugs may be caused by direct action on the heart and the peripheral vasculature, or by disturbance of cardiovascular regulation. The action of propofol on autonomic cardiovascular control mechanisms is not yet clear. Previous studies (1–5) evaluating the influence of propofol on the baroreceptor reflex using vasoactive drugs, found inconsistent results. Other investigators (6–8) have tried to determine the action of propofol on the autonomic nervous system by frequency domain analysis of cardiovascular signals. These studies are confronted with the problem that respiration contributes importantly to heart rate fluctuations (9–11); breathing depth and frequency cannot be sufficiently controlled in anesthetized subjects breathing spontaneously. Mechanical ventilation guarantees the control of respiration; however, its hemodynamic effects are different from those of spontaneous breathing. These circumstances enhance the problems already seen in the use of heart rate variability as an indicator of sympathetic and parasympathetic activity (12).

We designed this study to evaluate the autonomic cardiocirculatory control independently of the direct influence of respiration, and without the need of altering the hemodynamic baseline conditions. The approach is completely noninvasive and assesses the dynamic interaction of hemodynamic variables, as well as the effects of the carotid baroreceptor reflex on cardiac and blood pressure control.

Our investigation is based on the phenomenon that stimulation of the carotid baroreceptors at frequencies >0.15 Hz creates vagally transmitted oscillations in heart rate, independently of the effects of respiration (13,14) but only minimal oscillations in blood pressure (15,16) (Fig. 1). Baroreflex stimulation, at frequencies of 0.1 Hz or less, acts via sympathetic and parasympathetic efferentes and creates oscillations in heart rate, as well as in systolic blood pressure (SBP), and diastolic blood pressure (DBP) (15,17). Spontaneous fluctuations in blood pressure around 0.1 Hz are significantly correlated with sympathetic efferent activity to the peripheral vasculature (15,18–21). In accordance with this phenomenon, several investigators (15,22) found that the oscillations in blood pressure, generated by stimulation of baroreceptors at 0.1 Hz, represent the sympathetically mediated effect of baroreflex activity on the vessels.



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  		Figure 1. Exemplary power spectra of hemodynamic variables registered in an awake subject in supine position during frequency-controlled breathing at 0.25 Hz with and without neck suction. Fluctuations in RR intervals >0.15 Hz are mainly mediated by vagal activity, fluctuations in RR intervals <0.15 Hz reflect the effects of vagal and sympathetic activity on the heart. Breathing at 0.25 Hz is associated with a typical respiratory peak in the spectra of systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as RR intervals. Blood pressure fluctuations around 0.1 Hz are mediated by sympathetic activity to the vessels (left). Neck suction at 0.2 Hz (middle) creates fluctuations in RR intervals at 0.2 Hz of similar magnitude to the respiratory fluctuations, and only minimal fluctuations in blood pressure. Neck suction at 0.1 Hz (right) generates marked fluctuations in RR intervals (decreased scale of the y axis), as well as in blood pressure.

 
With these considerations in mind, we evaluated the dynamic autonomic cardiovascular regulation during propofol anesthesia in mechanically ventilated patients, focussing especially on the heart rate and blood pressure responses to peripheral baroreceptor stimulation.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
We studied 20 ASA physical status I patients (11 men, 9 women, mean age 37 ± 6.6 yr) scheduled for lumbar disk surgery. The study was approved by our local ethics committee and all subjects gave their written, informed consent to participate. On the preoperative afternoon, patients underwent a 3-min control registration after a resting period of approximately 15 min. Electrocardiogram (Sirecust 302D; Siemens, Erlangen, Germany), noninvasive blood pressure (Finapres; Ohmeda, Louisville, CO), and respiration (inductance plethysmograph, Respitrace system; Ambulatory Monitoring, Ardsley, NY) were registered while the subjects were breathing at a fixed frequency of 0.25 Hz. These measurements were performed after training of the breathing pattern to guarantee a stable breathing frequency and to avoid unintentional hyperventilation. During pilot experiments patients were often not able to perform frequency-controlled breathing with simultaneous neck suction in an adequate manner. Therefore, it was necessary to compare patients to a control group (13 men, 7 women, mean age 34 ± 4.0 yr) who underwent the measurement procedure in the awake state after an appropriate training period. In the control group, the baseline recording without neck suction and two 3-min recordings during neck suction at a frequency of 0.1 Hz and 0.2 Hz were performed. Neck suction was performed via a lead collar connected to a vacuum cleaner. Sinusoidal pressure fluctuations were created by a computer-controlled, mechanical pressure-release mechanism. The pressure was continuously monitored and kept in the range of 0 to -30 mm Hg.

Patients were premedicated with 20–30 mg oral clorazepate on the preoperative night. After infusion of 500 mL of isotonic crystalloid solution, anesthesia was induced with 2.5 mg/kg propofol and muscle relaxation was achieved with 0.1 mg/kg vecuronium. Immediately after the induction, an infusion of 0.1 mg · kg · min propofol IV was started. Patients were tracheally intubated with a tracheal tube lubricated with lidocaine solution and ventilated with 40% oxygen in air at a frequency rate of 15/min with an inspiration/expiration ratio of 1:1. End-tidal carbon dioxide tension was maintained at 35 mm Hg (Capnomac Ulima; Datex Instrumentarium Corp., Helsinki, Finland). After 20 min and during steady-state conditions, a 3-min baseline recording without neck suction, and two 3-min recordings during neck suction at a frequency of 0.1 Hz and 0.2 Hz were performed. Immediately after the recordings, a venous blood sample was collected at the contralateral forearm for the measurement of the plasma propofol concentration by high pressure liquid chromatography with fluorescence detection, according to a previously published method modified by our group (23). Each patient’s body was covered, and rectal temperature was always >36.0°C at the end of the measurements.

All signals were relayed to a 12-bit analog-to-digital converter and sampled at 1000 Hz on a personal computer, by using a program we designed based on commercially available software (Lab-VIEW; National Instruments, Austin, TX). R waves, SBP and DBP were automatically detected and RR intervals were calculated. Additionally, the signals were inspected visually and checked for artifacts and heterotopic beats. No correction of data was necessary in our subjects. Time series were computed from the RR intervals, SBP, DBP, neck chamber pressure, and the respiratory signal.

Stationarity of each period was checked by the reverse arrangement test described by Bendat and Piersol (24). Data were resampled at 4 Hz by using a moving 500-ms wide rectangular window (25). Each record was divided into three 50% overlapping segments. After direct current offset subtraction, removal of residual linear trends, and application of a Hanning window, discrete Fourier analysis was performed for each segment, and the power spectra computed. A smooth estimate of the power spectrum of each record was obtained as an average of these three spectra (24). The area under the curve was calculated for the following frequency bands: total frequency (<0.4 Hz), low frequency (0.04 to <0.15 Hz), components corresponding to the frequencies of neck suction at 0.2 Hz (0.175 to <0.225 Hz), and respiration at 0.25 Hz (0.225 to <0.275 Hz), provided that the squared coherence between signals was significant. Coherence function was calculated as a measure of the linear relationship between input and output by using six 50% overlapping windows. A squared coherence >0.53 was interpreted as a sign of stable phase shift (26), indicating a significant relationship between input and output. The relationship between variables of interest was evaluated by calculating the magnitudes and phases of the complex transfer functions (24).

Statistical analysis was performed by using commercially available software (SPSS for Windows 9.0; SPSS, Chicago, IL). The data were checked for normal distribution by using the Lilliefors modification of the Kolmogorov-Smirnov test. The results of spectral power analysis were normally distributed after logarithmic transformation. Normally distributed data are presented as mean ± SD, and were compared by using a general linear model procedure (repeated measures analysis of variance), and the Student’s t-test for unpaired data with adjustment of the {alpha} error, as appropriate. Nonparametric statistics were used to compare the values of transfer function magnitude (reported as median [10%, 90% percentiles]) between groups. A P < 0.05 was considered significant. The ß error was determined to be 0.3 for the comparison of the hemodynamic baseline values between groups, (assuming an effect size of approximately 0.65), and to be 0.2 for the comparison of the spectral power components, (effect size approximately 0.8). Under the condition that a phase shift of at least 0.5 rad was of interest, the probability of committing a ß error in the within-group comparison of phases was approximately 0.1.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Measurement procedures were successfully performed in all subjects. No patient required additional anesthetic or vasoactive drugs during anesthesia induction and the measurement period. Hemodynamic data and results of power spectral analysis are reported in Table 1.


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  		Table 1. Mean Values of RR Intervals and Blood Pressure, and Results of Power Spectral Analysis
 
Respiratory fluctuations of RR intervals decreased markedly during anesthesia, whereas low frequency (LF) power and total power of RR interval variability remained stable. This phenomenon was related to major fluctuations in blood pressure and RR intervals located at 0.055 ± 0.012 Hz (exemplary registration in Figure 2). Coherence analysis revealed a highly significant linear relationship between these fluctuations in RR intervals and SBP or DBP in 17 and 18 subjects, respectively (squared coherence 0.91 ± 0.08 and 0.94 ± 0.06), with a phase delay of 2.19 ± 0.32 rad between SBP and RR intervals and of 2.87 ± 0.19 rad between DBP and RR intervals. Thus, the LF fluctuations in SBP and DBP preceded the fluctuations in RR intervals by 5.7 ± 0.99 s and 7.9 ± 1.6 s, respectively.



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  		Figure 2. Exemplary registration of hemodynamic variables and their power spectra during propofol anesthesia and mechanical ventilation at 0.25 Hz. Fluctuations in RR intervals, as well as in blood pressure are superimposed by major underdampened oscillations at 0.057 Hz. AU = arbitrary units.

 
The temporal relationships of the spontaneous hemodynamic fluctuations at 0.1 Hz are demonstrated in Figure 3. In the awake state, the phase shift between the 0.1 Hz fluctuations in DBP or SBP, and RR intervals was identical between the study group (-2.17 ± 0.26 rad and -1.38 ± 0.38 rad, respectively) and the control group (-2.05 ± 0.42 rad and -1.30 ± 0.34 rad, respectively). During anesthesia, the phase shift between the spontaneous fluctuations in blood pressure and RR intervals at 0.1 increased significantly, regardless of whether the registration was performed without neck suction or with neck suction at 0.2 Hz (Figure 3). Neck suction at 0.1 Hz reinforced the spontaneous fluctuations at 0.1 Hz; however, it did not change the phase relationship between DBP and RR intervals (-2.90 ± 0.33 rad), and between SBP and RR intervals (-2.16 ± 0.49 rad).



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  		Figure 3. Phase relationships (reported in radians) between spontaneous fluctuations in blood pressure and respiratory rate (RR) intervals at 0.1 Hz in the patients in the awake state during spontaneous breathing at 0.25 Hz (left), during anesthesia ventilated mechanically at 0.25 Hz (middle), and during anesthesia with mechanical ventilation at 0.25 Hz and simultaneous neck suction at 0.2 Hz (right). RR intervals are computed at zero radians. The counter-clockwise position of systolic blood pressure (SBP) and diastolic blood pressure (DBP), with respect to the RR intervals, indicates that the fluctuations of blood pressure precede those of the RR intervals by the reported phase shifts. During anesthesia, the phase shifts between oscillations in blood pressure and RR intervals at 0.1 Hz increase significantly compared with the awake state. Thus, the oscillations of RR intervals at 0.1 Hz lag behind the oscillations of SBP and DBP by approximately 2.2 s and 3.5 s, respectively, in the awake state, and by 3.3 s and 4.4 s, respectively, during anesthesia. This phenomenon is not affected by simultaneous neck suction at 0.2 Hz. ** P < 0.01 vs the awake state.

 
Neck suction at 0.2 Hz was related to a slight increase in mean RR intervals in the awake state, as well as during anesthesia, whereas SBP and DBP remained unaffected. Neck suction at 0.2 Hz created fluctuations in RR intervals at 0.2 Hz that were markedly decreased during anesthesia, compared with the awake control values (Table 1). The coherence between neck chamber pressure and fluctuations in RR intervals at 0.2 Hz was significant in all subjects of the control group, but significant only in 11 subjects during anesthesia. In these subjects, the median of the transfer function magnitude between neck chamber pressure and RR intervals was significantly decreased to approximately 3% of the median of the awake control values (Figure 4).



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  		Figure 4. Magnitude of the transfer functions between neck chamber pressure and hemodynamic variables during neck suction at 0.2 Hz (left) and 0.1 Hz (right) in the awake state (control group) and during anesthesia (study group). Acting mainly via vagal activity, 0.2-Hz neck suction generates fluctuations in RR intervals, but only minimal fluctuations in heart rate. Neck suction at 0.1 Hz acts via parasympathetic and sympathetic efferents and generates marked fluctuations in RR intervals and in blood pressure. During anesthesia, the heart rate and blood pressure response to baroreceptor stimulation is markedly depressed. The box plots indicate medians and 10, 25, 75, and 90 percentiles. Pdia = diastolic blood pressure; Psys = systolic blood pressure.

 
The predominant fluctuations of RR intervals were located at significantly lower frequencies during neck suction at 0.2 Hz (0.038 ± 0.018 Hz) than during anesthesia without neck suction (P < 0.001). Because these fluctuations were partially located beyond the LF range, LF power decreased; however, total power of RR intervals remained stable, thus signalizing an unchanged variance of the signal.

The effect of neck suction at 0.1 Hz on hemodynamic fluctuations was markedly decreased during anesthesia. Coherence analysis revealed a significant linear relationship between stimulation of baroreceptors at 0.1 Hz and fluctuations in SBP (10 subjects), DBP (nine subjects), and RR intervals (11 subjects) during anesthesia, compared with 18 subjects of the control group. The median values of the transfer function magnitude between fluctuations in neck chamber pressure and in hemodynamic fluctuations were decreased to 7% (RR intervals), 26% (SBP), and 44% (DBP) of the median awake control values (Figure 4). Phase analysis revealed a phase shift of 1.40 ± 0.82 rad between fluctuations in neck chamber pressure and RR intervals at 0.1 Hz, that was significantly different from that observed in the awake control group (2.77 ± 0.33 rad; P < 0.001). Because a decrease in neck chamber pressure causes an increase in carotid transmural pressure, it is necessary to subtract one-half a period to obtain the phase shift between baroreceptor stimulation and RR interval fluctuations. Thus, neck suction preceded RR interval fluctuations at 0.1 Hz by approximately 0.6 s in the awake control group and by approximately 2.8 s during anesthesia. The phase shift between neck suction and fluctuations in blood pressure showed a wide scattering during anesthesia. Whereas the mean phase shift between fluctuations in neck chamber pressure and SBP was similar in the study group and the control group (-1.99 ± 1.08 rad vs -2.19 ± 0.48 rad), the mean phase shift between neck chamber pressure and DBP increased during anesthesia (-2.20 ± 1.44 rad vs -1.21 ± 0.56 rad, P < 0.05). Plasma propofol concentrations in blood samples, drawn immediately after hemodynamic recordings, were 1609 ± 432 ng/mL.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
There were three main results of this study. The vagally mediated heart rate response to cyclic peripheral baroreflex stimulation was markedly depressed during propofol anesthesia. The blood pressure response to cyclic baroreceptor stimulation at 0.1 Hz was significantly diminished during anesthesia. Propofol anesthesia was associated with marked underdampened hemodynamic fluctuations in the LF range.

Recent studies evaluating baroreflex activity reported varying effects of propofol on autonomic cardiovascular control; several authors observed unchanged baroreflex activity in animals (27), as well as in humans (1,28). Other investigators found various degrees of baroreflex depression (2,3,5,29,30) or different responses of the parasympathetic and the sympathetic limb of the baroreflex arch (4). Different study designs may contribute to these controversial results (spontaneous breathing vs controlled breathing via mask or endotracheal airway; different baseline values of heart rate and blood pressure during anesthesia). Most authors agree with the interpretation that propofol shifts the baroreflex response curve to the left (1,2,27,28,30).

All previous studies evaluated the open-loop gain of arterial baroreceptors as a static response to a hemodynamic pertubation. Our study investigated the dynamic response of the cardiovascular feedback system without the necessity of altering hemodynamic baseline conditions, and evaluated the baroreflex-mediated heart rate response, as well as the blood pressure response. This approach may give additional information about cardiovascular control mechanisms and might help to interpret the clinically relevant hemodynamic effects of a drug. Because the effects of spontaneous respiration and cyclic baroreflex stimulation are linearly transmitted by vagal activity in the high frequency range (13), our methodological approach allowed the assessment of the vagally mediated baroreflex response independently of the influence of respiration.

We found a markedly diminished dynamic cardiac baroreflex response during propofol anesthesia, despite mean SBP and DBP values being identical in the awake control group and in the anesthetized study group, thus giving evidence for a depressed vagally mediated baroreflex response, and confirming the results of previous studies observing an attenuated cardiac baroreflex response (2,5).

Several studies (2,4,5,31,32) reported a decrease in peripheral sympathetic activity during propofol anesthesia. Our results indicate an attenuated modulation of vascular tone to baroreceptor stimulation and demonstrate that the impairment of sympathetic activity during propofol anesthesia is also reflected by an impaired sympathetically mediated dynamic baroreflex effector response.

Studies (6–8) evaluating autonomic cardiovascular activity via power spectral analysis observed less reduction in LF power of RR intervals than in the respiratory component during propofol anesthesia and hypothesized whether sympathetic activity might be more preserved than parasympathetic activity or whether this phenomenon might simply represent the relatively increased contribution of the LF component to total power of heart rate variability. Our study reveals another mechanism that may be responsible for the reported preservation of LF-power—major hemodynamic oscillations with a mean cycle length of 18 s. Such underdampened long wavelength oscillations typically characterize a loss of stability in a feedback loop control system (33). Such a regulation may become unstable, when either the response curve or the delay time increases (33,34). It is well known that for respiratory control, periodic breathing is related to an increase in chemoreceptor responsiveness and to a prolonged circulation time (33,34). Madwed et al. (35) generated an unstable state of cardiovascular regulation under experimental conditions: spontaneous oscillations of blood pressure and heart rate at 0.05 Hz could be observed in dogs in the hypotensive hemorrhage state, presumably to a change in the baroreflex responsiveness with an inhibition of the vagal, and an activation of the sympathetic effector mechanism.

Our results do not indicate an increase in sympathetically mediated baroreflex responsiveness, because we found a significantly impaired blood pressure response to 0.1-Hz neck suction during anesthesia. However, we observed a delay in the baroreflex-mediated cardiocirculatory control system. Besides the fact that the latency between fluctuations in blood pressure and RR intervals at 0.055 Hz was markedly prolonged compared with physiological baroreflex mechanisms, we observed a significantly increased latency between the spontaneous fluctuations in blood pressure and RR intervals at 0.1 Hz during anesthesia. Spontaneous RR interval fluctuations at 0.1 Hz are often interpreted as created by baroreflex mechanisms (36–38). Even when the phase analysis does not differentiate between feed-forward and feed-backward mechanisms, our findings indicate a change in the closed-loop operation of the cardiovascular control during propofol anesthesia in mechanically ventilated subjects. This interpretation is supported by the observation that the phase shift between baroreceptor stimulation at 0.1 Hz and fluctuations in RR intervals and DBP was significantly prolonged during anesthesia.

During 0.2-Hz neck suction, the LF oscillations of RR intervals shifted to even lower frequencies. This can be explained by the phenomenon that intrinsic LF fluctuations can be modulated by oscillations of the autonomic nervous system at other frequencies (frequency-selective entrainment) (15,39).

The performance of frequency-controlled breathing during simultaneous neck suction requires an adequate training period, and pilot experiments showed that patients were often not able to control breathing during simultaneous neck suction. Therefore, we decided to design this study as an externally controlled study (40) and to perform the recordings with simultaneous neck suction in an awake control group (medical colleagues). Although the characteristics of both groups were similar, mean SBP and respiratory fluctuations in SBP were increased in the study group in the awake state, presumably caused by mental stress to the unusual situation. However, the other hemodynamic baseline values, as well as the results of phase analysis in the awake state at 0.1 Hz, were identical in both groups. The possible weakness of an externally controlled study may have been counteracted by the fact that the findings without neck suction were to be analyzed by a repeated measures design (internal control).

Besides the effects of propofol, the entire anesthesia regimen, including the effects of mechanical ventilation, may have affected our study results. We used vecuronium as a muscle relaxant with minimal autonomic and cardiovascular side effects. An influence of endotracheal intubation on autonomic activity cannot be eliminated. Neck suction per se might influence autonomic nervous response by creating an irritating stimulus to the trachea. However, neither heart rate nor blood pressure increased during the procedure, making a direct sympathetic stimulation unlikely. In addition, we used topical anesthesia of the tracheal mucosa in an effort to minimize unwanted side effects of neck suction during anesthesia.

Because the effects of propofol on autonomic cardiovascular control may vary with the central depressant activity of propofol, it may be the subject of future studies to evaluate the effect of different propofol doses on the hemodynamic control, and to relate these findings to measures of the depth of anesthesia.

In conclusion, we found a markedly depressed vagally mediated heart rate response, as well as an impaired blood pressure response to cyclic baroreceptor stimulation during propofol anesthesia. Our results demonstrate further, a delay in the baroreflex effector responses during anesthesia. These disturbances of the baroreflex feedback loop were accompanied by underdampened hemodynamic oscillations in the LF range, indicating an irregular dynamic behavior of cardiovascular regulation and suggesting a loss of stability of cardiocirculatory control during propofol anesthesia.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Samain E, Marty J, Gauzit R, et al. Effects of propofol on baroreflex control of heart rate and on plasma noradrenaline levels. Eur J Anaesthesiol 1989; 6: 321–6.[ISI][Medline]
  2. Ebert TJ, Muzi M, Berens R, et al. Sympathetic responses to induction of anesthesia in humans with propofol or etomidate. Anesthesiology 1992; 76: 725–33.[ISI][Medline]
  3. Larsen B, Büch U, Wilhelm W, Larsen R. Effects of propofol and fentanyl on the baroreceptor reflex in geriatric patients. Anästhesiol Intensivmed Notfallmed Schmerzther 1994; 29: 408–12.[Medline]
  4. Ebert TJ, Muzi M. Propofol and autonomic reflex function in humans. Anesth Analg 1994; 78: 369–75.[ISI][Medline]
  5. Sellgren J, Ejnell H, Elam M, et al. Sympathetic muscle nerve activity, peripheral blood flows, and baroreceptor reflexes in humans during propofol anesthesia and surgery. Anesthesiology 1994; 80: 534–44.[ISI][Medline]
  6. Scheffer GJ, Ten Voorde BJ, Karemaker JM, et al. Effects of thiopentone, etomidate and propofol on beat-to-beat cardiovascular signals in man. Anaesthesia 1993; 48: 849–55.[ISI][Medline]
  7. Galletly DC, Buckley DH, Robinson BJ, Corfiatis T. Heart rate variability during propofol anaesthesia. Br J Anaesth 1994; 72: 219–20.[Abstract/Free Full Text]
  8. Robinson BJ, Buyck HCE, Galletly DC. Effect of propofol on heart rate, arterial pressure and digital plethysmograph variability. Br J Anaesth 1994; 73: 167–73.[Abstract/Free Full Text]
  9. Hirsch JA, Bishop B. Respiratory sinus arrhythmia in humans: how breathing pattern modulates heart rate. Am J Physiol 1981; 241: H620–9.[Abstract/Free Full Text]
  10. Saul JP, Berger RD, Albrecht P, et al. Transfer function analysis of the circulation: unique insights into cardiovascular regulation. Am J Physiol 1991; 261: H1231–45.[Abstract/Free Full Text]
  11. Brown TE, Beightol LA, Koh J, Eckberg DL. Important influence of respiration on human R-R interval power spectra is largely ignored. J Appl Physiol 1993; 75: 2310–7.[Abstract/Free Full Text]
  12. Eckberg DL. Sympathovagal balance: a critical appraisal. Circulation 1997; 96: 3224–32.[Free Full Text]
  13. Cross SJ, Cowie MR, Rawless JM. Mutual interactions of respiratory sinus arrhythmia and the carotid baroreceptor-heart rate reflex. Clin Sci 1992; 82: 139–45.[Medline]
  14. Bernardi L, Bianchini B, Spadacini G, et al. Demonstrable cardiac reinnervation after human heart transplantation by carotid baroreflex modulation of RR interval. Circulation 1995; 92: 2895–903.[Abstract/Free Full Text]
  15. Bernardi L, Hayoz D, Wenzel R, et al. Synchronous and baroceptor-sensitive oscillations in skin microcirculation: evidence for central autonomic control. Am J Physiol 1997; 273: H1867–78.[Abstract/Free Full Text]
  16. Sunagawa K, Ikeda Y, Kawada T, et al. Dynamic control of arterial blood pressure by the sympathetic baroreflex. Fundam Clin Pharmacol 1998; 12 (Suppl 1): 23s–28s.
  17. Båth E, Lindblad LE, Wallin BG. Effects of dynamic and static neck suction on muscle nerve sympathetic activity, heart rate and blood pressure in man. J Physiol 1981; 311: 551–64.[Abstract/Free Full Text]
  18. Preiss G, Polosa C. Patterns of sympathetic neuron activity associated with Mayer waves. Am J Physiol 1974; 226: 724–30.[Free Full Text]
  19. Pagani M, Lombardi F, Guzzetti S, et al. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res 1986; 59: 178–93.[Abstract/Free Full Text]
  20. Malliani A, Pagani M, Lombardi F, Cerutti S. Cardiovascular neural regulation explored in the frequency domain. Circulation 1991; 84: 482–92.[Abstract/Free Full Text]
  21. Pagani M, Montano N, Porta A, et al. Relationship between spectral components of cardiovascular variabilities and direct measures of muscle sympathetic nerve activity in humans. Circulation 1997; 95: 1441–8.[Abstract/Free Full Text]
  22. Bjurstedt H, Rosenhammer G, Tydén G. Cardiovascular responses to changes in carotid sinus transmural pressure in man. Acta Physiol Scand 1975; 94: 497–505.[ISI][Medline]
  23. Plummer GF. Improved method for the determination of propofol in blood by high-performance liquid chromatography with fluorescence detection. J Chromatogr 1987; 421: 171–6.[ISI][Medline]
  24. Bendat JS, Piersol AG. Random data: analysis and measurement procedures. 2nd ed. New York: Wiley, 1986.
  25. Berger RD, Akselrod S, Gordon D, Cohen RJ. An efficient algorithm for spectral analysis of heart rate variability. IEEE Trans Biomed Eng 1986; 33: 900–4.[ISI][Medline]
  26. Taylor JA, Carr DL, Myers CW, Eckberg DL. Mechanisms underlying very-low-frequency RR-interval oscillations in humans. Circulation 1998; 98: 547–55.[Abstract/Free Full Text]
  27. Sellgren J, Biber B, Henriksson B-Å, et al. The effects of propofol, methohexitone and isoflurane on the baroreceptor reflex in the cat. Acta Anaesthesiol Scand 1992; 36: 784–90.[ISI][Medline]
  28. Cullen PM, Turtle M, Prys-Roberts C, et al. Effect of propofol anesthesia on baroreflex activity in humans. Anesth Analg 1987; 66: 1115–20.[Abstract/Free Full Text]
  29. Blake DW, Jover B, McGrath BP. Haemodynamic and heart rate reflex responses to propofol in the rabbit: comparison with althesin. Br J Anaesth 1988; 61: 194–9.[Abstract/Free Full Text]
  30. Rocchiccioli C, Saad MA, Elghozi J-L. Attenuation of the baroreceptor reflex by propofol anesthesia in the rat. J Cardiovasc Pharmacol 1989; 14: 631–5.[ISI][Medline]
  31. Robinson BJ, Ebert TJ, O’Brien TJ, et al. Mechanisms whereby propofol mediates peripheral vasodilation in humans. sympathoinhibition or direct vascular relaxation? Anesthesiology 1997; 86: 64–72.[ISI][Medline]
  32. Hoka S, Yamaura K, Takenaka T, Takahashi S. Propofol-induced increase in vascular capacitance is due to inhibition of sympathetic vasoconstrictive activity. Anesthesiology 1998; 89: 1495–1500.[ISI][Medline]
  33. Mackey MC, Glass L. Oscillation and chaos in physiological control systems. Science 1977; 197: 287–9.[Abstract/Free Full Text]
  34. Khoo MCK, Kronauer RE, Strohl KP, Slutsky AS. Factors inducing periodic breathing in humans: a general model. J Appl Physiol 1982; 53: 644–59.[Abstract/Free Full Text]
  35. Madwed JB, Albrecht P, Mark RG, Cohen RJ. Low-frequency oscillations in arterial pressure and heart rate: a simple computer model. Am J Physiol 1989; 256: H1573–9.[Abstract/Free Full Text]
  36. deBoer RW, Karemaker JM, Strackee J. Hemodynamic fluctuations and baroreflex sensitivity in humans: a beat-to-beat model. Am J Physiol 1987; 253: H680–9.[Abstract/Free Full Text]
  37. Toska K, Eriksen M, Walløe L. Short-term control of cardiovascular function: estimation of control parameters in healthy humans. Am J Physiol 1996; 270: H651–60.[Abstract/Free Full Text]
  38. Cooke WH, Hoag JB, Crossman AA, et al. Human responses to upright tilt: a window on central autonomic integration. J Physiol 1999; 517: 617–28.[Abstract/Free Full Text]
  39. Kitney RI, Fulton T, McDonald AH, Linkens DA. Transient interactions between blood pressure, respiration and heart rate in man. J Biomed Eng 1985; 7: 217–24.[ISI][Medline]
  40. Bailar III JC, Louis TA, Lavori PW, Polansky M. Studies without internal control. In: Bailar JC III, Mosteller F, eds. Medical uses of statistics. 2nd ed. Boston, MA: NEJM Books, 1992: 105–23.
Accepted for publication July 24, 2000.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press