Original Contributions Effects of Three Anesthetic Induction Techniques on Heart Rate Variability Terry W. Latson, MD,* S. Maire McCarroll, MB, BCh, FFARCSI,? M. Andrew Mirhej,$ Vernon A. Hyndman,§ Charles W. Whitten, MD,11 James M. Lipton, MD# Department at Dallas,
*Associate
Professor
tvisiting Assistant Anesthesiology SMedical
Student
OBiomedical (IAssistant
of Anesthesiology Professor
of
III
Engineering Professor
Specialist
of Anesthesiology
#Professor of Physiology, Research ciate Professor of Anesthesiology
Asso-
Address reprint requests to Dr. Latson at the Department of Anesthesiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas,
TX 75235-8894, USA. Dr. Latson was supported in part by an Institutional Research Grant from Southwestern Medical School. Parts of this material were presented at the Annual Meeting of the American Society of Anesthesiologists, Las Vegas, October 1% 23, 1990. Received for publication September 5, 199 1; revised manuscript accepted for publication January 10, 1992. 0 1992 Butter-worth-Heinemann J. Clin. Anesth.
4:265-276,
1992.
of Anesthesiology, Dallas,
Cniversity
of Texas
Southwestern
Medical
Center
TX.
Study Objective: To investigate the effects of diff erent clinical induction techniques on heart rate variability (HRV). Design: Two studies are reported. Study 1 prospectively compared the effects of two induction techniques (etomidate vs. thiopental sodium) known to have widely disparate effects on cardiovascular reflexes. Study 2 specifically investigated whether the vagotonic effects of sufentanil cause an increase in vagally mediated HRI’. Setting: Electi7le .surgery in a university-affiliated hospital. Patients: Study I: 18 ASA physical .ctatus I patients having minor surgery; Study 2: 10 ASA physical status III and IV patients having cardiac surgery. Interventions: In Study I, anesthesia was induced with either etomidate 0.3 mglkg or thiopental sodium 4 mglkg with 6OYo nitrous oxide in oxygen. In Study 2, anesthesia was induced with a sufentanil infusion (total dose 2.9 * 0.2 pglkg). Measurements and Main Results: The electrocardiogram-derived heart rate signal was subjected to power spectral analysis (similar to electroencephalopraphic analysis) to obtain measurements of (1) absolute HRV power [units of (beats per minute}21 within defined frequency ranges (HRV co = power between 0 and 0.125 Hz; HRV,, = power between 0.126 and 0.5 Hz; HRV,, = HRV,, f HRV,,) and (2) normalized HRV power (the percentage of total power) within these same frequency ranges [e.g., %HRVn, = (HRVJHRV,,) x 1 OO%]. In Study 1, both techniques caused large reductions in HRV,,. The reduction caused by the thiopental sodium technique ( - 89% 2 2%) significantly exceeded that caused by the etomidate technique ( - 58% 5 13%, p < 0.02). In Study 2, sufentanil decreased absolute power measurements of vagally mediated HRV (- 69 2 12 change in HRV,,) but increased corresponding normalized measurements of vagally mediated HRV (90%> 2 30% increase in %HR V,,). Conclusions: In Study I, the greater reduction in HRV with the thiopental sodium technique provides evidence that the depressant effects of anesthetics on HRV are related in part to their effects on cardiovascular reflexes. However, th.e significant depression in HRV caused by the etomidate technique suggests that mechanisms other than baroreflex depression (e.g., impaired consciousness) also are important in these depressant effects. In Study 2, the decrease in HRV,, caused by sufentanil documents that absolute power measurements of vagally mediated HRV are not correlated with changes in J. Clin. Anesth.,
vol. 4, July/August
1992
265
Original Conttibutions
Keywords: Anesthesia,
general; anesthetics; autonomic nervous system; baroreflexes; etomidate; heart rate: sufentanil; thiopental sodium.
Introduction I’kie term
heart r-de ztaridnlity (HKV) describes small oscillations in heart rate (HK) caused by the interaction of’ multiple regulatory influences on the sinus node. Power spectral analysis of’ HKV can provide noninvasive measurements of‘ autonomic nervous system activity.’ i ‘I‘his analysis measures both the amplitude and frequency of’ these HK oscillations [similar to power spectral analysis of’ the electroencephalogram (EEG)]. Oscillations occurring at dif‘ferent frequencies are associated with the acLivity of‘ different autonomic reflexes. Oscillations occurring at frequencies higher than about 0.123 Hz (i.(,.. a repetirion period OF 8 seconds or less) are mediated primarily by parasympathetic reflexes associated with sinus arrhythmia).’ L respiration (t.~., the respiratory Changes in the amplitude of’ these high-frequency oscillations have been correlated with changes in parasyrnOscillations occurring at lowetpathetic activity.& l’requencies at-e thought to be tnediared predominarttl! reflexes,‘,’ although pharmacologic by sympathetic blocking studies suggest that parasympathetic reflexes also are involved. Changes in the amplitude of’these lowf’requency oscillations have been cot-related with changes in sympathelic activit)..‘.’ HKV analysis may have itnportanr applications to the study of‘al~erations in autonomic activity caused by anes1hesia and surgery. Prior studies in the anesthesia literature have related alterations in HKV to both depth of‘ anesthesia”-” and changes in central autonomic outflow.*lC’ 1’However, important questions retnain regarding the application of’HRV analysis to anesthesia studies. One essential question is whether dif’f’erent anesthetic drugs have different effects on HKV. All prior studies isoflurane,“’ enHurane,* with anesthetics (halothane,” thiopental sodium, 11and the combination sevoflurane,li of’ fentanyl midazolam, and pancuronium*) have shown reductions in all f‘requency components of- HKV that wet-e measured during general anesthesia. However, all of these studies were limited to single anesthetic techniques, they were performed in varied study populations, and they used different analytical methods. Making meaningf’ul contparisons of’ the effects of‘ different an-
266
J. Clin. Anesth.,
vol. 4, July/August
1992
es1 hrtic-s on the basis 01’these pre\ ious srudies is. therr>fore, dif‘ficult. :\tiothet~ itnportattf and related queslion i5 the eliofog!’ of the reductions in HKV caused bv anesthetic-~ Prior studies itt t~rtNttl~.sthe/izud human sttbjects have related changes in HKV to several mechanisms: alteratiotr~ in svmpathetic and parasympathetic activit!., ’ ’ changes itt baroreflex sertsitivit\,.” I1 tmpaired cerebral function (resulting f’rom brain injury), Ii I0 interrupted au1ononiic neuropath~~.‘” 1” TOW reflex pathwavs. I7 and autonomic. extent to which each of‘ these mechanisms tnav be itt\,olvetl with anesthetic effects art HKV is ttnc-lea;.. If’ im l~unc tion associated witlt the loss 01 paired cerebral ~~otis~~iottsttess c-;ittsed b\ ~general attesthrsia ltas
*Associate
Professor
tvisiting Assistant Anesthesiology SMedical
Student
OBiomedical (IAssistant
of Anesthesiology Professor
of
III
Engineering Professor
Specialist
of Anesthesiology
#Professor of Physiology, Research ciate Professor of Anesthesiology
Asso-
Address reprint requests to Dr. Latson at the Department of Anesthesiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas,
TX 75235-8894, USA. Dr. Latson was supported in part by an Institutional Research Grant from Southwestern Medical School. Parts of this material were presented at the Annual Meeting of the American Society of Anesthesiologists, Las Vegas, October 1% 23, 1990. Received for publication September 5, 199 1; revised manuscript accepted for publication January 10, 1992. 0 1992 Butter-worth-Heinemann J. Clin. Anesth.
4:265-276,
1992.
of Anesthesiology, Dallas,
Cniversity
of Texas
Southwestern
Medical
Center
TX.
Study Objective: To investigate the effects of diff erent clinical induction techniques on heart rate variability (HRV). Design: Two studies are reported. Study 1 prospectively compared the effects of two induction techniques (etomidate vs. thiopental sodium) known to have widely disparate effects on cardiovascular reflexes. Study 2 specifically investigated whether the vagotonic effects of sufentanil cause an increase in vagally mediated HRI’. Setting: Electi7le .surgery in a university-affiliated hospital. Patients: Study I: 18 ASA physical .ctatus I patients having minor surgery; Study 2: 10 ASA physical status III and IV patients having cardiac surgery. Interventions: In Study I, anesthesia was induced with either etomidate 0.3 mglkg or thiopental sodium 4 mglkg with 6OYo nitrous oxide in oxygen. In Study 2, anesthesia was induced with a sufentanil infusion (total dose 2.9 * 0.2 pglkg). Measurements and Main Results: The electrocardiogram-derived heart rate signal was subjected to power spectral analysis (similar to electroencephalopraphic analysis) to obtain measurements of (1) absolute HRV power [units of (beats per minute}21 within defined frequency ranges (HRV co = power between 0 and 0.125 Hz; HRV,, = power between 0.126 and 0.5 Hz; HRV,, = HRV,, f HRV,,) and (2) normalized HRV power (the percentage of total power) within these same frequency ranges [e.g., %HRVn, = (HRVJHRV,,) x 1 OO%]. In Study 1, both techniques caused large reductions in HRV,,. The reduction caused by the thiopental sodium technique ( - 89% 2 2%) significantly exceeded that caused by the etomidate technique ( - 58% 5 13%, p < 0.02). In Study 2, sufentanil decreased absolute power measurements of vagally mediated HRV (- 69 2 12 change in HRV,,) but increased corresponding normalized measurements of vagally mediated HRV (90%> 2 30% increase in %HR V,,). Conclusions: In Study I, the greater reduction in HRV with the thiopental sodium technique provides evidence that the depressant effects of anesthetics on HRV are related in part to their effects on cardiovascular reflexes. However, th.e significant depression in HRV caused by the etomidate technique suggests that mechanisms other than baroreflex depression (e.g., impaired consciousness) also are important in these depressant effects. In Study 2, the decrease in HRV,, caused by sufentanil documents that absolute power measurements of vagally mediated HRV are not correlated with changes in J. Clin. Anesth.,
vol. 4, July/August
1992
265
Original Conttibutions
Keywords: Anesthesia,
general; anesthetics; autonomic nervous system; baroreflexes; etomidate; heart rate: sufentanil; thiopental sodium.
Introduction I’kie term
heart r-de ztaridnlity (HKV) describes small oscillations in heart rate (HK) caused by the interaction of’ multiple regulatory influences on the sinus node. Power spectral analysis of’ HKV can provide noninvasive measurements of‘ autonomic nervous system activity.’ i ‘I‘his analysis measures both the amplitude and frequency of’ these HK oscillations [similar to power spectral analysis of’ the electroencephalogram (EEG)]. Oscillations occurring at dif‘ferent frequencies are associated with the acLivity of‘ different autonomic reflexes. Oscillations occurring at frequencies higher than about 0.123 Hz (i.(,.. a repetirion period OF 8 seconds or less) are mediated primarily by parasympathetic reflexes associated with sinus arrhythmia).’ L respiration (t.~., the respiratory Changes in the amplitude of’ these high-frequency oscillations have been correlated with changes in parasyrnOscillations occurring at lowetpathetic activity.& l’requencies at-e thought to be tnediared predominarttl! reflexes,‘,’ although pharmacologic by sympathetic blocking studies suggest that parasympathetic reflexes also are involved. Changes in the amplitude of’these lowf’requency oscillations have been cot-related with changes in sympathelic activit)..‘.’ HKV analysis may have itnportanr applications to the study of‘al~erations in autonomic activity caused by anes1hesia and surgery. Prior studies in the anesthesia literature have related alterations in HKV to both depth of‘ anesthesia”-” and changes in central autonomic outflow.*lC’ 1’However, important questions retnain regarding the application of’HRV analysis to anesthesia studies. One essential question is whether dif’f’erent anesthetic drugs have different effects on HKV. All prior studies isoflurane,“’ enHurane,* with anesthetics (halothane,” thiopental sodium, 11and the combination sevoflurane,li of’ fentanyl midazolam, and pancuronium*) have shown reductions in all f‘requency components of- HKV that wet-e measured during general anesthesia. However, all of these studies were limited to single anesthetic techniques, they were performed in varied study populations, and they used different analytical methods. Making meaningf’ul contparisons of’ the effects of‘ different an-
266
J. Clin. Anesth.,
vol. 4, July/August
1992
es1 hrtic-s on the basis 01’these pre\ ious srudies is. therr>fore, dif‘ficult. :\tiothet~ itnportattf and related queslion i5 the eliofog!’ of the reductions in HKV caused bv anesthetic-~ Prior studies itt t~rtNttl~.sthe/izud human sttbjects have related changes in HKV to several mechanisms: alteratiotr~ in svmpathetic and parasympathetic activit!., ’ ’ changes itt baroreflex sertsitivit\,.” I1 tmpaired cerebral function (resulting f’rom brain injury), Ii I0 interrupted au1ononiic neuropath~~.‘” 1” TOW reflex pathwavs. I7 and autonomic. extent to which each of‘ these mechanisms tnav be itt\,olvetl with anesthetic effects art HKV is ttnc-lea;.. If’ im l~unc tion associated witlt the loss 01 paired cerebral ~~otis~~iottsttess c-;ittsed b\ ~general attesthrsia ltas
