Ultradian Cardiac Rhythms in Surgical Intensive Care Unit Patients DARRELL M. WILSON, BS, DANIEL F. KRIPKE, MD, DOUGLAS K. MCCLURE, MA, AND A. GERSON GREENBURG, MD
Several reports have suggested that heart rate may be regulated by an ultradian biological rhythm with a period of about 90-100 min. Blood pressure and heart rate were collected from 10 Surgical Intensive Care patients at 5-min intervals and analyzed by computer. No 90-min rhythms were found, indicating this rhythm has no significant influence on heart rate or blood pressure in postsurgical patients.
INTRODUCTION
During sleep there is a regular rhythmic alternation about every 90-100 min between rapid eye movement (REM) and non-rapid eye movement (non REM) sleep. During REM slight increases in heart rate and blood pressure as well as larger increases in the variability of heart rate and blood pressure have been described (1-3), but a specific 90-100-min rhythm in sleep cardiovascular variability has not been described. There have been, however, some suggestions of 90—100-min rhythms in cardiovascular function. Orr and colleagues (4) have described 90-min rhythms in the heart rate of waking subjects. Orr et al. used a com-
From the School of Medicine, University of California, San Diego, and the San Diego Veterans Administration Hospital. This work was partially supported by the Medical Research Service of the Veterans Administration and by PHS MH 21350. Address reprint requests to: Dr. Daniel F. Kripke, Veterans Administration Hospital (116), 3350 La Jolla Village Drive, San Diego, CA 92161. Received for publication August 16, 1976; final revision received April 21, 1977. 432
plex demodulation technique to detect heart rate rhythms, but their phaseamplitude demodulates showed little consistency among subjects, and their recolored spectra showed no reliable peaks at the predicted frequency, lending some uncertainty to their conclusions. Kuzel (5) described "ultradian" cycles in heart rate and cardiac arrhythmias recorded from patients in a coronary intensive care unit; however, these "cycles" were rare and also variable. In contrast, in an unpublished study, one of us (DFK) found no significant 90-min rhythm in the heart rate or the heart rate variability of five normal ambulant subjects recorded for 96 hr each. Also heart rate 90-min rhythms were not significant in an isolation study that did detect rhythms in EEG (6). Thus, the importance of 90-min rhythms in cardiovascular regulation remains in doubt. Were 90-min rhythms a significant factor in cardiovascular variation in postoperative patients undergoing continuous monitoring, an understanding of these rhythms would be essential for proper interpretation of the trends observed during clinical monitoring. An
Psychosomatic Medicine Vol. 39, No. 6 (November-December
Copyright « 1977 by the American Psychoso Published by Elsevier North-Holland, Inc.
1977)
ULTRADIAN CARDIAC RHYTHMS
important 90-min rhythm might create acute variations in blood pressure and heart rate, which could, conceivably, create clinical concern. To see if 90-min rhythms are present and, indeed, significant in monitored patients, 10 subjects were studied in our Surgical Intensive Care Unit (SICU). METHODS
Data Collection The bed stations in our SICU are instrumented to transmit heart rate and the systolic blood pressure to a Hewlett-Packard (HP) 2100 computer system operating with the HP MEDACE computerized patient monitoring system. Those patients studied all had brachial intraarterial catheters. Arterial pressure wave forms were obtained through HP 1280 pressure transducers, and the signals were processed and displayed by HP 7089A blood pressure monitors. Systolic (peak) pressures were electronically detected and transmitted to the computer. The electrocardiogram (ECG) was recorded through chest leads and processed by HP 7803A ECG monitors. An internal cardiotachometer circuit derived an analog of heart rate, which was also transmitted to the computer. The data windows for these detection circuits are complex, yielding effective sampling intervals of about 5 sec. The computer interrogated each monitored parameter every minute. At 5-min intervals, the high and low samples were discarded (an artifact screening algorithm), and the remaining three data samples were averaged. This screening algorithm had been incorporated into the system to improve the reliability of estimates of the 5-min means of heart rate and blood pressure; however, the inclusion of this algorithm made evaluation of short-term heart rate and blood pressure variability impossible with the available system. The 5-min averages were recorded on magnetic tape for later off-line analyses.
Patient Selection Over a 2-month period, 16 subject were selected prospectively, provided that arterial pressure was to be monitored for at least 12 hr, and that no major
procedures were planned. All recorded blood pressures and heart rates were graphed and examined by the authors to define those time series with a low percentage of obviously defective recordings (e.g., those with prolonged periods of blood pressures of zero in a living patient). From the 16 recorded, the 10 most technically perfect recordings were selected. These 10 recordings averaged only one defective data point in 100. Defective samples were corrected by linear interpolation from adjacent measurements. A total of 174.3 hr were analyzed (12-28 hr per subject). Fifty-nine percent of the data selected were recorded between 1800 hr in the evening and 0600 hr in the morning. The SICU was darkened from 2200 to 0600, but it is not known when the patients slept. Nine of the patients had undergone major surgery within the prior few days, and the tenth was being monitored for normal pressure hydrocephalus. All 10 subjects were male, with a mean age of 57 (range 42-77).
Analyses For each recording, the mean and the linear trend were removed and the autocovariance function was computed for 0-36 lags (3 hr). The variance spectrum was derived from this autocovariance function. The spectral resolution was 4 cycles per day (CPD). Each variance spectrum was "hanned" and normalized to a standardized total variance (7). The 10 spectra were then averaged. Since the spectral peaks of ultradian rhythms are rather broad, relatively low spectral resolution was desired to improve reliability (8). From previous studies, a spectral peak in the band including 12-20 CPS (72-120 min cycles) was prospectively predicted.
RESULTS
On visual inspection, blood pressure and heart rate plots contained no impressive 90-min cycles. Averaged spectra for blood pressure and heart rate are shown in Fig 1. Clearly, most of the variance was in the lowest frequencies, and the variance fell smoothly as frequency increased. There were plainly no mean spectrum peaks in
Psychosomatic Medicine Vol. 39, No. 6 (November-December 1977)
433
DARRELL M. WILSON ET AL.
20
r
Average Heart Rote Average Blood Pressure
CYCLES PER DAY Fig 1. The averaged spectra for heart rate and blood pressure show no spectral peak between 12 and 20 CPD.
the 12-20-CPD range. Only 1 of the 10 individual subjects had any peak between 12 and 20 CPD. In this subject, the heart-rate variance at 16 CPD approached the variance at 0 CPD. No other spectrum showed even a hint of 12-20-CPD rhythms. DISCUSSION
There are several possible explanations for the absence of 90-100-min rhythms in these heart rate and blood pressure recordings. The SICU lacks the quiet, controlled environment characteristic of most 434
rhythm studies. The unit is a single room (19.5 m x 7.3 m), which can accommodate up to nine patients and many staff. The unit is noisy. Cardiovascular responses to activities in the unit and ministrations to the patients might have masked any endogenous blood pressure or heart rate rhythms. Possibly, the SICU environment disturbs REM sleep sufficiently to eliminate it as a source of variance in the 12-20-CPD frequency range, although we entertained the possibility that a heart-rate rhythm would be seen in waking patients. All of the patients had serious maladies and nine had postsurgical trauma, which might have obscured or suppressed any rhythm that
Psychosomatic Medicine Vol. 39, No. 6 (November-December 1977)
ULTRADIAN CARDIAC RHYTHMS
might normally be present. Therefore, these findings should not be generalized to other populations. Another possibility is that there are no endogenous 90-min cardiovascular rhythms substantial enough to predominate over background variance. Those previous studies reporting 90-min rhythms in heart rate had failed to utilize inferential methods distinguishing random from systematic oscillations, or had reported "rhythms" in only an insignificant proportion of subjects. The cardiovascular system may be sufficiently well-insulated from the neural cycles that affect mental function to make any influence of the REM-nonREM cycle trivial. Although our monitoring instrumentation was subject to various potential errors, it seems unlikely any technical problem could have biased the spectra of all subjects. The MEDACE algorithm
samples only a few sec from each 5 min. However, were sampling too infrequent, one would have expected aliasing to produce much more variance in the higher frequencies. The spectra seem to confirm the adequacy of the sampling system. SUMMARY
No spectral peak was found in the 12-20-CPD range, indicating that 90-100-min rhythms were not a significant or substantial source of variance in SICU blood pressure and heart rate monitoring. These rhythms need be no clinical concern. Further research is needed to clarify conflicting reports suggesting that 90-100-min rhythms in heart rate and blood pressure might be substantial in other circumstances.
REFERENCES 1. Snyder F, Hobson J, Morrison D, Goldfrank F: Changes in respiration, heart rate, and systolic blood pressure in human sleep. J Appl Physiol 19:417-422, 1964 2. Burdick J, Brinton G, Goldskin L, Laszlo M: Heart rate variability in sleep and wakefulness. Cardiology 55:79-83, 1970 3. Khatri I, Freis E: Hemodynamic changes during sleep. J Appl Physiol 2:867-873, 1967 4. Orr W, Hoffman H: A 90-min cardiac biorhythm: methodology and data analysis using modified periodograms and complex demodulation. IEEE Trans Biomed Eng BME 21:130-143, 1974 5. Kuzel M: Cirdacian and ultradian rhythms identified in temperature, blood pressure, heart rate, dysrhythmias, and susceptibility cycles following acute myocardial infarction. Masters thesis in nursing, DePaul University, 1973 6. Kripke D: An ultradian rhythm associated with perceptual deprivation and REM sleep. Psychosom Med 34:221-234, 1972 7. Halberg F, Panofsky H: Thermovariance spectra: method and clinical illustration. Exp Med Surg 19:284-309, 1961 and Thermovariance spectra: simplified computational example and other methodology. Ibid. 323-338 8. Kripke D: Ultradian rhythms in sleep and wakefulness, in E Weitzman (ed.), Sleep Research, Vol I. New York, Spectrum, 1974, pp. 305-325
Psychosomatic Medicine Vol. 39, No. 6 (November-December 1977)
435
Several reports have suggested that heart rate may be regulated by an ultradian biological rhythm with a period of about 90-100 min. Blood pressure and heart rate were collected from 10 Surgical Intensive Care patients at 5-min intervals and analyzed by computer. No 90-min rhythms were found, indicating this rhythm has no significant influence on heart rate or blood pressure in postsurgical patients.
INTRODUCTION
During sleep there is a regular rhythmic alternation about every 90-100 min between rapid eye movement (REM) and non-rapid eye movement (non REM) sleep. During REM slight increases in heart rate and blood pressure as well as larger increases in the variability of heart rate and blood pressure have been described (1-3), but a specific 90-100-min rhythm in sleep cardiovascular variability has not been described. There have been, however, some suggestions of 90—100-min rhythms in cardiovascular function. Orr and colleagues (4) have described 90-min rhythms in the heart rate of waking subjects. Orr et al. used a com-
From the School of Medicine, University of California, San Diego, and the San Diego Veterans Administration Hospital. This work was partially supported by the Medical Research Service of the Veterans Administration and by PHS MH 21350. Address reprint requests to: Dr. Daniel F. Kripke, Veterans Administration Hospital (116), 3350 La Jolla Village Drive, San Diego, CA 92161. Received for publication August 16, 1976; final revision received April 21, 1977. 432
plex demodulation technique to detect heart rate rhythms, but their phaseamplitude demodulates showed little consistency among subjects, and their recolored spectra showed no reliable peaks at the predicted frequency, lending some uncertainty to their conclusions. Kuzel (5) described "ultradian" cycles in heart rate and cardiac arrhythmias recorded from patients in a coronary intensive care unit; however, these "cycles" were rare and also variable. In contrast, in an unpublished study, one of us (DFK) found no significant 90-min rhythm in the heart rate or the heart rate variability of five normal ambulant subjects recorded for 96 hr each. Also heart rate 90-min rhythms were not significant in an isolation study that did detect rhythms in EEG (6). Thus, the importance of 90-min rhythms in cardiovascular regulation remains in doubt. Were 90-min rhythms a significant factor in cardiovascular variation in postoperative patients undergoing continuous monitoring, an understanding of these rhythms would be essential for proper interpretation of the trends observed during clinical monitoring. An
Psychosomatic Medicine Vol. 39, No. 6 (November-December
Copyright « 1977 by the American Psychoso Published by Elsevier North-Holland, Inc.
1977)
ULTRADIAN CARDIAC RHYTHMS
important 90-min rhythm might create acute variations in blood pressure and heart rate, which could, conceivably, create clinical concern. To see if 90-min rhythms are present and, indeed, significant in monitored patients, 10 subjects were studied in our Surgical Intensive Care Unit (SICU). METHODS
Data Collection The bed stations in our SICU are instrumented to transmit heart rate and the systolic blood pressure to a Hewlett-Packard (HP) 2100 computer system operating with the HP MEDACE computerized patient monitoring system. Those patients studied all had brachial intraarterial catheters. Arterial pressure wave forms were obtained through HP 1280 pressure transducers, and the signals were processed and displayed by HP 7089A blood pressure monitors. Systolic (peak) pressures were electronically detected and transmitted to the computer. The electrocardiogram (ECG) was recorded through chest leads and processed by HP 7803A ECG monitors. An internal cardiotachometer circuit derived an analog of heart rate, which was also transmitted to the computer. The data windows for these detection circuits are complex, yielding effective sampling intervals of about 5 sec. The computer interrogated each monitored parameter every minute. At 5-min intervals, the high and low samples were discarded (an artifact screening algorithm), and the remaining three data samples were averaged. This screening algorithm had been incorporated into the system to improve the reliability of estimates of the 5-min means of heart rate and blood pressure; however, the inclusion of this algorithm made evaluation of short-term heart rate and blood pressure variability impossible with the available system. The 5-min averages were recorded on magnetic tape for later off-line analyses.
Patient Selection Over a 2-month period, 16 subject were selected prospectively, provided that arterial pressure was to be monitored for at least 12 hr, and that no major
procedures were planned. All recorded blood pressures and heart rates were graphed and examined by the authors to define those time series with a low percentage of obviously defective recordings (e.g., those with prolonged periods of blood pressures of zero in a living patient). From the 16 recorded, the 10 most technically perfect recordings were selected. These 10 recordings averaged only one defective data point in 100. Defective samples were corrected by linear interpolation from adjacent measurements. A total of 174.3 hr were analyzed (12-28 hr per subject). Fifty-nine percent of the data selected were recorded between 1800 hr in the evening and 0600 hr in the morning. The SICU was darkened from 2200 to 0600, but it is not known when the patients slept. Nine of the patients had undergone major surgery within the prior few days, and the tenth was being monitored for normal pressure hydrocephalus. All 10 subjects were male, with a mean age of 57 (range 42-77).
Analyses For each recording, the mean and the linear trend were removed and the autocovariance function was computed for 0-36 lags (3 hr). The variance spectrum was derived from this autocovariance function. The spectral resolution was 4 cycles per day (CPD). Each variance spectrum was "hanned" and normalized to a standardized total variance (7). The 10 spectra were then averaged. Since the spectral peaks of ultradian rhythms are rather broad, relatively low spectral resolution was desired to improve reliability (8). From previous studies, a spectral peak in the band including 12-20 CPS (72-120 min cycles) was prospectively predicted.
RESULTS
On visual inspection, blood pressure and heart rate plots contained no impressive 90-min cycles. Averaged spectra for blood pressure and heart rate are shown in Fig 1. Clearly, most of the variance was in the lowest frequencies, and the variance fell smoothly as frequency increased. There were plainly no mean spectrum peaks in
Psychosomatic Medicine Vol. 39, No. 6 (November-December 1977)
433
DARRELL M. WILSON ET AL.
20
r
Average Heart Rote Average Blood Pressure
CYCLES PER DAY Fig 1. The averaged spectra for heart rate and blood pressure show no spectral peak between 12 and 20 CPD.
the 12-20-CPD range. Only 1 of the 10 individual subjects had any peak between 12 and 20 CPD. In this subject, the heart-rate variance at 16 CPD approached the variance at 0 CPD. No other spectrum showed even a hint of 12-20-CPD rhythms. DISCUSSION
There are several possible explanations for the absence of 90-100-min rhythms in these heart rate and blood pressure recordings. The SICU lacks the quiet, controlled environment characteristic of most 434
rhythm studies. The unit is a single room (19.5 m x 7.3 m), which can accommodate up to nine patients and many staff. The unit is noisy. Cardiovascular responses to activities in the unit and ministrations to the patients might have masked any endogenous blood pressure or heart rate rhythms. Possibly, the SICU environment disturbs REM sleep sufficiently to eliminate it as a source of variance in the 12-20-CPD frequency range, although we entertained the possibility that a heart-rate rhythm would be seen in waking patients. All of the patients had serious maladies and nine had postsurgical trauma, which might have obscured or suppressed any rhythm that
Psychosomatic Medicine Vol. 39, No. 6 (November-December 1977)
ULTRADIAN CARDIAC RHYTHMS
might normally be present. Therefore, these findings should not be generalized to other populations. Another possibility is that there are no endogenous 90-min cardiovascular rhythms substantial enough to predominate over background variance. Those previous studies reporting 90-min rhythms in heart rate had failed to utilize inferential methods distinguishing random from systematic oscillations, or had reported "rhythms" in only an insignificant proportion of subjects. The cardiovascular system may be sufficiently well-insulated from the neural cycles that affect mental function to make any influence of the REM-nonREM cycle trivial. Although our monitoring instrumentation was subject to various potential errors, it seems unlikely any technical problem could have biased the spectra of all subjects. The MEDACE algorithm
samples only a few sec from each 5 min. However, were sampling too infrequent, one would have expected aliasing to produce much more variance in the higher frequencies. The spectra seem to confirm the adequacy of the sampling system. SUMMARY
No spectral peak was found in the 12-20-CPD range, indicating that 90-100-min rhythms were not a significant or substantial source of variance in SICU blood pressure and heart rate monitoring. These rhythms need be no clinical concern. Further research is needed to clarify conflicting reports suggesting that 90-100-min rhythms in heart rate and blood pressure might be substantial in other circumstances.
REFERENCES 1. Snyder F, Hobson J, Morrison D, Goldfrank F: Changes in respiration, heart rate, and systolic blood pressure in human sleep. J Appl Physiol 19:417-422, 1964 2. Burdick J, Brinton G, Goldskin L, Laszlo M: Heart rate variability in sleep and wakefulness. Cardiology 55:79-83, 1970 3. Khatri I, Freis E: Hemodynamic changes during sleep. J Appl Physiol 2:867-873, 1967 4. Orr W, Hoffman H: A 90-min cardiac biorhythm: methodology and data analysis using modified periodograms and complex demodulation. IEEE Trans Biomed Eng BME 21:130-143, 1974 5. Kuzel M: Cirdacian and ultradian rhythms identified in temperature, blood pressure, heart rate, dysrhythmias, and susceptibility cycles following acute myocardial infarction. Masters thesis in nursing, DePaul University, 1973 6. Kripke D: An ultradian rhythm associated with perceptual deprivation and REM sleep. Psychosom Med 34:221-234, 1972 7. Halberg F, Panofsky H: Thermovariance spectra: method and clinical illustration. Exp Med Surg 19:284-309, 1961 and Thermovariance spectra: simplified computational example and other methodology. Ibid. 323-338 8. Kripke D: Ultradian rhythms in sleep and wakefulness, in E Weitzman (ed.), Sleep Research, Vol I. New York, Spectrum, 1974, pp. 305-325
Psychosomatic Medicine Vol. 39, No. 6 (November-December 1977)
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