Desflurane Inhibits U Wave in Electrocardiogram

Desflurane inhibits U wave
Original Article
Acta Cardiol Sin 2005;21:214-22
Electrophysiology
Desflurane Inhibits U Wave in
Electrocardiogram
Chern-En Chiang,1 Chieh-hung Li,2 Shih-Kuei Peng,2 Chu-Pin Lo,3 Juan-Ming Yuan3 and Hsiang-Ning Luk2,3
Background: Volatile anesthetics inhibit cardiac transmembrane ionic currents and intracellular ionic activity and
exert antiarrhythmic actions. Among electrocardiogram (ECG) waveforms, the effect of volatile anesthetics on U
wave has never been studied. The aim of the present observational study was to evaluate the possible effect of
desflurane on U wave in anesthetized patients.
Methods: Peri-operative ECG tracings (lead II) were recorded and analyzed from 24 gynecologic patients
(American Society of Anesthesiologists (ASA), class 1). Anesthesia was routinely induced with thiopental, fentanyl
and succinylcholine and maintained with desflurane (1 to 1.5 minimal alveolar concentration (MAC)) and O2. U
wave amplitude (Uamp) was manually measured from amplified ECG records.
Results: Discernible U wave in 24 patients varied in amplitude (64 ± 24 mV). U wave was three times larger when
heart rate increased to maximum during tracheal intubation. Similarly, Uamp was augmented (285% ± 58% of the
control) in extrasystolic beats elicited by tracheal intubation. Desflurane (1 to 1.5 MAC) significantly and reversibly
suppressed Uamp (a decrease by 60 ± 24 mV, n = 24, p < 0.05).
Conclusions: The suppressive effect of desflurane on Uamp might be explained by its inhibitory effects on
transmembrane ionic currents, intracellular calcium load and delayed afterdepolarizations. Our results support a
contributory role of afterpotentials in the genesis of U wave.
Key Words:
U wave · ECG · Desflurane · Volatile anesthetics
INTRODUCTION
afterpotentials have been correlated with the occurrence
of U wave.7 It should be mentioned that U wave can also
be observed in normal healthy subjects. Therefore, U
wave might be explained by a common cellular mechanism shared by both physiologic and pathologic conditions. Since volatile anesthetics are known for their
cellular electropharmacological effects and antiarrhythmic actions, 8,9 we therefore evaluated the possible
effects of desflurane on U wave in anesthetized patients.
The origin of U wave has been explained by several
hypotheses, although it remains is dispute up to now.1-4
For example, inhomogeneous prolongation of QT interval in epicardium, endocardium and M-cell layers may
provide a substrate for TU complex in pathologic condition. 5,6 In addition, in a computer simulation model,
Received: October 18, 2005 Accepted: December 23, 2005
1
Department of Cardiology, Taipei Veterans General Hospital and
National Yang-Ming University; 2Department of Anesthesiology,
Taichung Veterans General Hospital; 3Department of Applied
Mathematics, Providence University, Taiwan.
Address correspondence and reprint requests to: Dr. Hsiang-Ning Luk,
MD, MS, PhD, Associate Professor, BMMC, Providence University
and Taichung Veterans General Hospital, 160, Section 3, TaichungHarbor Road, Taichung 407, Taiwan. Tel: 886-4-2461-3371; Fax:
886-4-2461-3371; E-mail: [email protected]
Acta Cardiol Sin 2005;21:214-22
METHODS
From September 2004 to March 2005, 24 consecutive female patients receiving gynecological surgery
were included in this observational study. All patients
were otherwise healthy (American Society of Anesthesiologists (ASA) class I, from 20 to 63 years old) and
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Desflurane inhibits U wave
speed of 25 mm/s. The U wave was defined as a positive
deflection immediately following the T wave. The amplitudes and the duration of intervals of ECG waveforms
were measured manually by using calipers and magnifying lens by two independent anesthesiologists in order to
minimize the inter-observer variability. The amplitudes
of T wave (Tamp) and U wave (Uamp) were defined as the
absolute distance from the apex of the respective wave
to the isoelectric baseline. If T and U waves fused, the
Uamp was measured from the nadir of T-U complex to the
peak of U wave. The ratio of Uamp/Tamp was also analyzed. The duration of QT interval was measured from
start of Q wave to the end of T wave. If the descent of T
wave did not touch the baseline, the end of T wave was
determined by the intersection of slope of descent of T
wave and baseline. The duration of QU interval was
measured from the start of Q wave to the peak of U
wave. The preceding RR interval was measured and was
used to correct QT and QU using Bazett’s formula (QTc
neither of them had arrhythmia, electrolyte imbalance,
myocardial ischemia and infarction, cardiac hypertrophy
and cardiomyopathy, or cerebral hemorrhage. All subjects were in normal sinus rhythm and showed sizable U
wave in their electrocardiogram (ECG). Medical history,
physical examination, chest radiograph and biochemical
data revealed no remarkable abnormalities. None of the
patients was taking medications. The investigation conformed with the principles outlined in the Declaration of
Helsinki. This prospective, non-randomized clinical
study was approved by local institutional review committee. All patients gave their written informed consent.
Peri-operative ECG (lead II) was recorded using a
two-channel recorder and analyzed in all the patients
during anesthesia (study protocol, see Figure 1). The
limb lead electrodes were placed at left and right shoulders and the fifth intercostal space at the left axillary
line. All ECG recordings were amplified (5 mm/0.1 mV)
and all selected ECG strips were printed out at a paper
Figure 1. Study protocol. Lead II ECG tracings were recorded at different stages of anesthesia.
215
Acta Cardiol Sin 2005;21:214-22
Chern-En Chiang et al.
Table 1. Changes in ECG parameters by desflurane
and QUc).
Standard peri-operative monitoring was routinely instituted (blood pressure, ECG, end-tidal CO 2 , pulsed
arterial saturation). The induction of anesthesia was performed with fentanyl (1 to 2 mg/kg), thiamylal (4 to 6
mg/kg), and succinylcholine (1 to 2 mg/kg). After tracheal intubation was completed, anesthesia was maintained with desflurane (1 to 1.5 MAC) in the presence of
pure oxygen (0.5 L/min). Both the inspiratory and endexpiratory concentrations of desflurane were on-line
monitored with an agent analyzer. Muscle relaxation was
maintained with either atracurium or rocuronium. The
depth of anesthesia was monitored and adjusted by bispectral analysis, auditory evoked potential or autonomic
parameters. The results are expressed as the mean ±
standard deviation. Minimal and maximal values are indicated. Comparison of T-U changes before and after the
administration of desflurane were performed using paired samples t-test. Numbers in parentheses indicate 95%
confidence interval of difference (Table 1). To test the
difference, a p value < 0.05 was regarded as statistically
significant.
(n = 24)
Control
Age
(yr)
Weight
(kg)
Height
(cm)
RR interval
(ms)
Tamp
(µV)
Uamp
(µV)
Uamp/Tamp
QT
(ms)
QTc
(ms)
QU#
(ms)
QUc#
(ms)
Difference
41.1 ± 13.1 (20, 63)
56.0 ± 6.7 (40, 73)
158.6 ± 6.8 (148, 170)
819 ± 142
1026 ± 1150
428 ± 132
452 ± 131
64 ± 24
4±9
0.17 ± 0.10
0.01 ± 0.03
393 ± 350
447 ± 43
432 ± 280
442 ± 36
523 ± 410
553 ± 45
556 ± 200
544 ± 62
206 ± 152*
[142, 271]
23 ± 103
[-20, 67]
-60 ± 24*
[-50, -70]
-0.16 ± 0.10*
[-0.12, -0.21]
054 ± 36*
[38, 69]
10 ± 41
[-7, 27]
030 ± 18*
[13, 47]
-12 ± 58
[-66, 42]
Data are expressed as mean ± standard deviation.
* denotes p < 0.05
Numbers in parentheses indicate 95% confidence interval of
difference.
#n=7
RESULTS
Typical examples of U wave from 7 different patients are shown in Figure 2. In addition to appearing
immediately after the end of T wave, U wave sometimes
fused with T wave during bradycardia or encroached
into P wave during tachycardia. The demographic data
and ECG parameters of 24 gynecologic patients in this
observational study are summarized in Table 1. The size
of U wave was variable (64 ± 24 mV). Since U wave was
previously regarded as bradycardia-dependent, the size
of U wave was therefore compared at maximal and minimal values of heart rate during tracheal intubation. In 4
patients, the size of U waves was three times larger at
maximal heart rate than that at minimal one (300% ±
156%).
In 7 out of 24 patients, ventricular extrasystoles
were elicited by tracheal intubation during induction of
anesthesia. Figure 3 shows ECG tracings of such an example. The size of the U wave of the extrasystoles could
be augmented to 285% ± 58% of the control value before
induction of anesthesia (n = 7). The suppressive effect of
Acta Cardiol Sin 2005;21:214-22
Desflurane
desflurane (1 to 1.5 MAC) on U wave was recorded in
24 patients with discernible U wave. Figure 4 shows
such an example. In comparison to that of control
(pre-induction resting state), the amplitude of U wave
was dramatically and progressively decreased by desflurane. The overall suppressive effect of desflurane on
U wave is presented in Table 1. In addition to prolonging
the QT interval (54 ± 36 ms, p < 0.05), desflurane significantly decreased Uamp (60 ± 24 mV, p < 0.05). It is noted
that suppressive effect of desflurane on U wave was reversible when desflurane was gradually washed out from
the patient during emergence from anesthesia (Figure 5).
DISCUSSION
U wave in ECG is known to appear in certain
216
Desflurane inhibits U wave
Figure 2. Discernible U wave in ASA class 1 female patients. Lead II ECG tracings were recorded from 7 patients before anesthesia. Sizable U
wave was fused with T wave (panels A, F, G) or P wave (panel B). ECG waveforms were amplified (5 mm/0.1 mV), and all selected ECG strips were
printed out at a paper speed of 25 mm/s. In each panel, a representative U wave is indicated by an arrow.
substrate for abnormal TU complex, prolonged QT interval, and possibly the ventricular arrhythmias. 5,6 Such
theory might explain the large U wave in patients with
hypokalemia and ventricular hypertrophy, because both
conditions caused prolongation of the action potential
duration in cardiomyocytes. But this theory cannot explain the ischemia-related U wave because both ischemia
and hypoxia are expected to shorten the action potential.
Above all, the U wave can even become negative in polarity under the condition of myocardial ischemia. Such
change of inverted U wave cannot fully be explained by
pathologic conditions, such as electrolyte imbalance,
subarachnoid hemorrhage, myocardial ischemia, left
ventricular hypertrophy and cardiomyopathy. 10-14 It
should be mentioned, however, that U wave can also
appear in normal healthy subjects (up to 70% of prevalence). Thus, the genesis of U wave might be explained
by a common cellular mechanism in both pathologic and
physiologic conditions. A few hypotheses have been
proposed up to now, but none of them is overwhelmingly
persuasive. For example, inhomogeneous prolongation of
action potentials in ventricular myocytes might provide a
217
Acta Cardiol Sin 2005;21:214-22
Chern-En Chiang et al.
Figure 3. Extrasystoles-augmented U wave during tracheal intubation. In this patient with sizable U wave, ventricular extrasystoles occurred
immediately after tracheal intubation (panels A-D). The amplitudes of U wave following the extrasystoles (arrows) were much larger than those in
pre-anesthesia state and progressively decreased when the extrasystoles were replaced by sinus rhythm (panel E). Voltage scale: 5 mm/0.1 mV. Speed
scale: 25 mm/s.
Thus, it is plausible to hypothesize that the size of U
wave might be reflected by the status of intracellular calcium load on a beat-by-beat basis. In in-vitro studies,
volatile anesthetics inhibit transmembrane calcium current, reduce intracellular calcium activity and suppress
delayed afterdepolarizations.8,16,17,20,21 Our results favor
this hypothesis because desflurane could significantly
decrease U wave size in the present study (Figures 4, 5).
Other volatile anesthetics (e.g., isoflurane and sevoflurane), with shared similar cardiac cellular electropharmacological actions, also suppress U wave. 22,23
Therefore, the links between intracellular calcium load,
delayed afterdepolarizations, and U wave can be made.
Such link can be further supported by the fact that
sympathomimetics can increase U wave size in normal
healthy subjects.24 In addition, post-extrasystole U wave
augmentation has been demonstrated in patients with
right ventricular outlet-ventricular tachycardia which is
correlated with catecholamine, intracellular calcium and
triggered activity.25,26 Our results also show that U wave
the inhomogeneous prolongation of the action potential.
In the present study, we demonstrated that desflurane
suppressed U wave (Figures 4, 5) but did not shorten the
QT or QTc (Table 1). Instead, desflurane significantly
prolonged QT and QU intervals during anesthesia. In vitro experiments, volatile anesthetics depressed variable
cardiac ionic channels and delayed the late repolarization phase of the action potentials. 8,15-17 Clinical
studies also confirmed that volatile anesthetics, such as
desflurane, increased QT interval. 18,19 Therefore, it
seems that prolongation of the action potentials is not
prerequisite for the genesis of U wave in normal healthy
subjects, and the antagonizing action of desflurane on U
wave is not likely via reversing the prolongation of QT
interval.
In a computer simulation model, U wave was correlated with the afterpotentials. 7 It is well known that
afterpotentials or delayed afterdepolarizations are related
to intracellular calcium overload and activation of sodium-calcium exchange and transient inward current.
Acta Cardiol Sin 2005;21:214-22
218
Desflurane inhibits U wave
Figure 4. Suppressive effects of desflurane on U wave. A series of U wave changes from pre-anesthesia state (panel A) to those immediately after
tracheal intubation (panels B-D) and during maintenance of anesthesia (panels E-G). Arrow indicates an example of U wave in each tracing. It is
noted that U wave was completely suppressed by desflurane (panel G). Voltage scale: 5 mm/0.1 mV. Speed scale: 25 mm/s.
amplitude was increased at faster heart rate during tracheal intubation when sympathetic tone was enhanced.
We also demonstrated that high sympathetic tone elicited ventricular extrasystoles during tracheal intubation
while amplitude of U wave was increased (Figure 3).
Whether a protein kinase A-dependent signal transduction pathway is involved in the modulation of U
wave needs to be further studied.
It is surprising that such high prevalence of visible U
wave could be observed in female patients in our study
and in other normal healthy subjects (up to 70%). 24
Since our patients were categorized into ASA class I, the
common causes of pathologic U wave can be excluded.
The role of U wave in healthy subjects is not known so
far. However, our preliminary results show that patients
with sizable U wave are prone to develop ventricular
extrasystoles during induction of anesthesia (manuscript
in preparation). The arrhythmogenic role of sizable U
wave in patients during induction of anesthesia remains
to be explored. On the other hand, lack of ventricular
extrasystoles in such patients during maintenance of
anesthesia might be explained by the antiarrhythmic ac219
Acta Cardiol Sin 2005;21:214-22
Chern-En Chiang et al.
Figure 5. Reversible inhibitory effects of desflurane on U wave. (A): pre-anesthesia state; (B-D): progressive inhibition of U wave by desflurane
during maintenance of anesthesia; (E-F): recovery of suppressed U wave during emergence from anesthesia. Arrows indicate examples of U wave in
each tracing. Voltage scale: 5 mm/0.1 mV. Speed scale: 25 mm/s.
In conclusion, desflurane could suppress U wave in
healthy anesthetized female patients and might serve as a
pharmacological tool to further understand the origin of
U wave.
tions of volatile anesthetics via suppressing U waves. So
far, the potential clinical implication of the antiarrhythmic action of desflurane on U wave is not clear
yet.
Several limitations of the present study should be
noted. Due to practical limitation, lead II was used for
routine peri-operative ECG monitoring, which might not
reflect the real changes of U wave. U wave usually can
be best observed in precordial leads V2, V3 and V4 from
a complete 12-lead ECG. The confounding factors (such
as age, body weight, hemodynamic changes, duration of
anesthesia) were not analyzed in the present study due to
the small sample size.
Acta Cardiol Sin 2005;21:214-22
ACKNOWLEDGEMENTS
The grant for this research from Taichung (TCVGH946304C) and Taipei Veterans General Hospitals and
Providence University is highly appreciated. The authors thank Miss Mindy Lin for her devoted secretarial
work.
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Desflurane inhibits U wave
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Acta Cardiol Sin 2005;21:214-22
Original Article
Acta Cardiol Sin 2005;21:214−22
Desflurane 抑制心電圖的 U 波
江晨恩 1 李介宏 2 彭士魁 2 羅主斌 3 袁淵明 3 陸翔寧 2,3
台北市 台北榮民總醫院及陽明大學 心臟內科1
台中市 台中榮民總醫院 麻醉科2
台中縣 靜宜大學 應用數學系3
背景 揮發性麻醉劑可抑制心臟細胞細胞膜上的各種離子流及細胞內的離子活性，同時也
表現出其抗心律不整的藥理作用。然而，在心電圖所有的波型當中，唯有 U 波從未被研究
是否受到此類麻醉劑的影響。本觀察型的臨床研究就是要探討，在婦科病患的麻醉過程當
中，desflurane 對 U 波的影響。
方法 在 24 位健康的婦科病患 (美國麻醉醫學會分類的第一級)，於麻醉過程當中記錄並
分析其第二導程的心電圖。麻醉誘導的方式採用常規的藥物，包括 thiopental，fentanyl，
succinylcholine 三種藥物。麻醉維持期則以 desflurane (1 至 1.5 最小肺泡濃度) 及氧氣為主。
U 波幅度的大小是從放大的心電圖記錄紙以手工目視量取。
結果 在 24 位呈現 U 波的婦科病患當中，其平均幅度為 64 ± 24 µV。當進行氣管插管的
動作時，若病患的心跳因此而有明顯的增快，U 波的幅度可以隨心跳變快而增大 3 倍左右。
若病患此時出現短暫的心室性早期收縮，U 波的幅度也會變大，是麻醉前的 285% ± 58%。
在 24 位病患當中，desflurane (1 至 1.5 最小肺泡濃度）會顯著且可逆地抑制 U 波幅度的大
小 (減少 60 ± 24 µV，p < 0.05)。
結論 心電圖的 U 波會受到 desflurane 的抑制，可能是與其抑制心臟細胞膜的離子流、細
胞內的鈣離子活性及延遲性後去極化有關。本研究結果顯示，U 波的生成可能與後膜電位
的假說較有關聯。
關鍵詞：U 波、心電圖、desflurane、揮發性麻醉劑。
222