Journal of

Cardiothoracic and Vascular Anesthesia VOL 6, NO 6


EDITORIAL Heart Rate Variability

and Anesthesiology:


EART RATE variability (HRV) refers to small oscillations in heart rate associated with the activity of homeostatic autonomic reflexes.’ The “respiratory sinus arrhythmia” (RSA), which is the cyclical change in heart rate synchronous with respiration, is one component of HRV known to most physicians. However, other cyclical changes in heart rate at frequencies distinct from the respiratory frequency are well described. There is a current resurgence of interest in HRV among physiologists and physicians due to recent studies in which HRV measurements have been correlated with (1) the integrity and “balance” of sympathetic and parasympathetic reflexes’“; and (2) mortality following myocardial infarction.4 Clinical investigations involving HRV are not new. Hon and Lee described the use of fetal HRV as a qualitative measure of fetal distress in 1965.5 In that same year, McCrady et al suggested that changes in HRV (specifically, RSA) might provide an index of “anesthetic depth.“6 More recent clinical studies have focused on the use of HRV as a noninvasive monitor of autonomic reflex activity, and how alterations in such activity may be related to various disease processes.1*3 As a noninvasive monitor of autonomic reflex activity, there would appear to be numerous potential applications of HRV technology to the specialty of anesthesiology. The investigation by Estafanous et al7 reported in this issue of the Journal explores some of these potential applications. HRV is thought to result from the interplay of multiple homeostatic reflexes involved with respiration, blood pressure, venous return, regional vasomotor tone, and thermoregulation. Conditions affecting these reflexes will influence HRV (eg, postural changes, mental stress, impaired cerebral function, exercise, and several types of cardiovascular disease). Some insights into the reflex mechanisms involved with HRV have been provided by pharmacologic blocking studies (eg, with atropine, propranolol, or epidural anesthesia) and mathematical models of physiologic control systems.8s9 However, how these various reflex mechanisms interact for the genesis of HRV, either under normal or pathophysiologic conditions, is not well established. Although this lack of information regarding mechanisms is a significant limitation, it should not preclude appropriate observational studies. By analogy, there is limited understanding of the genesis of EEG waveforms, yet EEG analysis has had immense clinical application.



and VascularAnesthesia,


for Cautious


Currently, three major methodologies are used for analysis of HRV. The first involves measurements of statistical variability in R-to-R intervals between normal QRS complexes. This methodology is the most “repeatable” among different investigators because the measurement algorithms are simple and well defined (eg, the standard deviation of RR intervals over a given length of time). These methods have been used in large studies establishing correlations between HRV and mortality after myocardial infarction.4 The second major methodology is power spectral analysis, which measures both the frequency and amplitude of oscillations in heart rate. These HRV measurements are conceptually similar to power spectral measurements of the EEG, although the frequencies of interest are quite different (ie, up to 30 Hz for B waves in the EEG, versus up to 0.5 Hz for “high-frequency” HRV). These frequency-specific HRV measurements are believed to provide additional information about sympathetic versus parasympathetic reflex activity.’ The third major methodology involves measurements of the “complexity,” “entropy,” or “chaos” in the pattern of successive RR intervals.‘” This methodology is currently the least well investigated. Potential advantages include the diminished influence of infrequent noise, and ability to analyze “non-oscillatory” variations in heart rate, which may be related to the complex interactions of multiple physiologic control systems. Current research is dominated by studies using frequencyspecific measurements of HRV as a “noninvasive probe” of sympathetic and parasympathetic reflex activity. This methodology is used by Estafanous et al7 in the study reported in this issue of the Journal, as well as by Komatsu et ali’ in a study reported in a previous issue. Pharmacologic blocking studies suggest that heart rate oscillations occurring at frequencies higher than about 0.125 to 0.15 Hz (known as “high-frequency” HRV; predominantly a measure of RSA) are mediated almost exclusively by parasympathetic reflexes, whereas oscillations at lower frequencies (“lowfrequency” HRV) are mediated jointly by sympathetic and parasympathetic reflexes.8 Clinical studies have suggested that measures of high-frequency HRV may be useful as a qualitative index of parasympathetic reflex activity or “tone,” and that measures of low-frequency HRV may provide an

Key words: heart rate, autonomic

Vol6, No 6 (December), 1992: pp 647-650

reflexes, anesthesia, monitoring



index of sympathetic “tone.“‘.3 This conventional interpretation is based on observational experiments using (1) defined experimental interventions to perturb autonomic reflexes (eg, head-up tilt); and (2) examination of HRV in disease conditions thought to be associated with altered autonomic reflexes. Although this is undoubtedly a very simplistic interpretation of complex physiologic control mechanisms, it appears to have some clinical utility. Early studies involving anesthesia and HRV examined the depression of high-frequency HRV (ie, RSA) associated with general anesthesia. h.12All anesthetic techniques studied to date, with the possible exception of “pure” etomidate,9 have been shown to reduce HRV. This depression of HRV has been proposed as an indicator of anesthetic depth and postoperative recovery.12J3 Recent studies have suggested that use of HRV for monitoring anesthetic depth may not be as straightforward as initially hoped because (1) different anesthetic techniques have different effects on HRV,‘? and (2) the effects of surgical stimulation on HRV are complex, and may vary significantly with the anesthetic technique.” The articles by Komatsu et al*’ and Estafanous et al7 in the possible application of HRV the Journal illustrate measurements to the study of changes in sympathetic and parasympathetic “balance” caused by anesthetics. The work by Komatsu et al” was initially presented in abstract form in 1986 (Anesthesiology 65:A139), and represents one of the first studies in which the effects of anesthesia on both high-frequency and low-frequency HRV were examined. Despite some differences in methodology and anesthetic techniques, both studies demonstrate that narcotic induction causes an increase in the ratio of high-frequency HRV to low-frequency HRV. ‘J’ Stated another way, narcotic induction causes an increase in the proportion of total HRV power that resides in the high-frequency “parasympathetic” range. This relative increase in highfrequency HRV is consistent with the reported effects of potent narcotics on autonomic “balance” measured by more invasive techniques (ie, increased vagal tone and decreased sympathetic tone).lh Although both studies report an increase in the ratio of high-frequency to low-frequency HRV, the findings of the two studies do differ with respect to anesthetic effects on specific HRV power measurements. Whereas Estafanous et al’ found a significant decrease in only low-frequency HRV power, Komatsu et al” found a significant decrease in both high-frequency and low-frequency HRV power. In addition to differences in premeditation and specific induction techniques, these disparate findings may relate to differences involving measurement methods, ventilatory patterns at the time of postinduction measurements (which may affect high-frequency HRV), and autonomic responses to intubation. Another recent study in patients induced with sufentanil also reported decreases in both high-frequency and low-frequency HRV power.14 Recent studies in awake subjects suggest that interpretation of these changes in specific HRV power measurements may not be as straightforward as initially presumed. Al-


though preliminary studies suggested that changes in highfrequency and low-frequency HRV power provided qualitative measures of changes in parasympathetic and sympathetic “tone,” respectively, this interpretation may not be valid when the defined intervention is accompanied by a decrease in total HRV power.’ For instance, sympathetic activation caused by mental stress is accompanied by a decrease in “sympathetic” (ie, low-frequency) HRV power. This “paradoxical” decrease in low-frequency HRV power is thought to result from the decrease in total HRV power that accompanies mental stress. By analogy, because general anesthesia is usually accompanied by a decrease in total HRV power, it may be premature to assume that the decrease in high-frequency HRV power measured after narcotic inductioni’,‘” is indicative of a decrease in parasympathetic tone. Studies by Latson et ali4Js have suggested that additional effects of anesthetics on HRV related to loss of consciousness may be involved with these decreases in total HRV power. However, even under conditions where total HRV power is reduced, changes in the frequency distribution of HRV power (cg, the ratio of high-frequency HRV to low-frequency HRV) reported by Komatsu et al” and Estafanous et al’ appear to remain a qualitative measure of changes in sympathetic-parasympathetic balance.‘.ii These changes in the frequency distribution of HRV power arc now often reported using “normalized” measurements of HRV. These measurements are “normalized” to adjust for changes in total HRV power (eg, high-frequency HRV power divided by total HRV power), and, thus, represent the proportion of total HRV power in a specific frequency range independent of changes in total HRV power.’ The article by Estafanous et al7 in this issue explores another potential application for HRV in anesthesia: prcoperative assessment of autonomic “function,” and possible relations to the hemodynamic effects of anesthetics. The hemodynamic changes caused by anesthetics are mediated not only by their direct effects on vascular tone and myocardial function, but also by their effects on autonomic reflexes. Therefore, it is reasonable to expect that preoperative differences in autonomic function (similar to preoperative differences in myocardial function) might play a significant role in different hemodynamic responses to specific anesthetics among patients. Hemodynamic decompensation with administration of potent narcotics to patients with acute elevations in sympathetic tone (eg, hypovolemia, tamponade) is a recognized example of this phenomenon. However, the effects of more subtle alterations in autonomic function (ie, alterations not apparent from baseline hemodynamics) have received little attention. In this regard, it should be appreciated that many medical conditions other than diabetes are associated with variable degrees of autonomic dysfunction (eg, hypertension, advanced age, depressedventricular function, myocardial infarction, and various drug therapies). A study by Burgos et al” in 1989 was the first to systematically document that preoperative differences in autonomic function among elective surgical patients can



play a significant role in the hemodynamic effects of anesthetics. Using standard tests of autonomic function (eg, the Valsalva maneuver), these authors demonstrated an increased incidence of hypotension in diabetics with autonomic neuropathy. Recent investigations have extended these findings to autonomic dysfunction in nondiabetic patients undergoing both cardiacIs and noncardiac surgery.19 Using power spectral measurements of HRV, these latter studies documented an increased incidence of hypotension in patients with decreased HRV. The article by Estafanous et al7 is the first study to document that preoperative differences in autonomic function may influence the heart rate response to anesthetic administration. Patients who developed a greater than 20% decrease in mean heart rate with sufentanil induction had decreased high-frequency HRV prior to induction, and an increased ratio of low-frequency to high-frequency HRV. Using “conventional” interpretations of frequency-specific HRV measurements, these results suggest that patients with decreased parasympathetic reflex activity were more prone to develop a significant decrease in heart rate. Possible explanations for this observation include (1) patients with decreased parasympathetic reflex activity prior to induction were susceptible to greater augmentation in parasympathetic activity with sufentanil administration; (2) the effects of sufentanil on heart rate are more related to its sympatholytic effects than its vagotonic effects (ie, patients with decreased parasympathetic reflex activity were more reliant on sympathetic reflexes for heart rate control); and (3) the decreased parasympathetic HRV is simply a marker of autonomic dysfunction, with resultant blunting of reflex responses to sufentanil-induced hypotension. The present study does not identify which mechanism (or mechanisms) is involved. However, it remains an important observational study that relates preoperative differences in autonomic function to anesthetic effects. The results also suggest that HRV measurements could be used to identify up to 80% of patients prone to significant decreases in heart rate with a sufentanilivecuronium induction (with scopolamine pre-

medication). Prospective studies are needed to determine if this finding can be used to improve patient care. Other potential applications for HRV in anesthesiology include monitoring of regional anesthesia and identification of patients more susceptible to complicated postoperative outcomes. Pruett et al20 have shown decreases in HRV accompanying high levels of spinal anesthesia; application of this finding as a useful clinical monitor awaits further studies. Using measurements of approximate entropy (a “regularity” statistic), Fleischer et a121reported that perioperative reduction in HRV entropy may be associated with a worse outcome. Studies with larger numbers of patients that include comparisons with other techniques for measuring HRV are needed to substantiate this finding. Mounting evidence suggests that alterations in autonomic reflex activity occurring prior to, during, and after anesthesia and surgery may play an important role in perioperative morbidity. Because measurements of HRV offer potential as a noninvasive monitor of autonomic function, such measurements could play an important role in patient care. However, the measurement of HRV should not be considered an “established technology.” Many controversies involving both measurement techniques and interpretation remain. Studies to date are largely observational in nature, and the mechanisms responsible for observed alterations in HRV are poorly understood. In addition, because of the large number of factors that can influence HRV, the sensitivity and specificity of HRV measurements with relation to a specific phenomenon may be limited. Further studies are certainly needed. However, continuing advances in the study of HRV by investigators in other fields, as well as by anesthesiologists, provide reasons for cautious optimism. Terry W. Latson, MD

Associate Professor, Director Division of Cardiovascular/Thoracic Anesthesiology The University of Texas Southwest Medical Center Dallas, TX

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thetic and anesthetic agents on the respiration-heart rate response of dogs. Am J Vet Res 26:710-716, 1965 7. Estafanous FG, Brum JM, Ribeiro MP, et al: Analysis of heart rate variability to assess hemodynamic alterations following induction of anesthesia. J Cardiothoracic Vast Anesth 6:651-657, 1992 8. 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 59:178-193, 1986 9. Scheffer GJ: Neuro-cardiovascular control during anesthesia. Doctoral thesis, University of Amsterdam, Amsterdam, The Netherlands, 1990 10. Pincus SM, Gladstone IM, Ehrenkranz RA: A regularity statistic for medical data analysis. J Clin Monit 7:335-345,199l 11. Komatsu T, Kimura T, Sanchafa V, et al: Effects of fentanyldiazepam-pancuronim anesthesia on heart rate variability: a spectral analysis. J Cardiothoracic Vast Anesth 6:444-448, 1992


sinus arrhyth12. Donchin Y, Feld JM, Porges SW: Respiratory mia during recovery from isoflurane-nitrous oxide anesthesia. Anesth Analg 64:81 l-815, 1985 13. Pfeifer BL, Sernaker HL, Porges SW: Respiratory sinus arrhythmia: An index of anesthetic depth. Anesth Analg 67:S170, 1988 14. Latson TW. Mirhej A, McCarroll SM, et al: Effects of three anesthetic techniques on heart rate variability. J Clin Anesth 41265-276, 1992 1.5. Latson TW, Wiley J, O’Flaherty DN: Surgical stimulation significantly reduces the depression of autonomic reflexes caused by propofol. Anesthesiology 75:A85, 1991 16. Laubie M, Schmitt H: Action of the morphinometic agent, fentanyl, on the nucleas tractus solitarii and the nucleus ambiguus cardiovascular neurons, Europ J Pharm 67:403-412, 1980


17. Burgos LG. Ebert TJ, Asiddao C, et al: Increased intraoperative cardiovascular morbidity in diabetics with autonomic neuropathy. Anesthesiology 70591-597, 1989 18. Latson T, Sakai T, Whitten C: Autonomic reflex dysfunction in cardiac surgery patients may predict hypotension at induction. Anesth Analg 74:S174, 1992 19. Latson TW, Ashmore TH. Reinhart DJ, et al: Autonomic reflex dysfunction is associated with post-induction hypotension in both diabetic and non-diabetic patients. Anesthesiology 1992 (in press) 20. Pruett JK. Yodlowski EH, lntrons RPS, et al: The intluence of spinal anesthetics on heart rate variations. Pharmacol 105-55. 1991 21. Fleisher LA. Pincus SM, Rosenbaum SH: Approximate entropy (ApEn) as a correlate of postoperative cardiac dysfunction. Crit Care Med 2O:S22, 1992

Heart rate variability and anesthesiology: reasons for cautious optimism.

Journal of Cardiothoracic and Vascular Anesthesia VOL 6, NO 6 DECEMBER 1992 EDITORIAL Heart Rate Variability and Anesthesiology: H EART RATE var...
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