Propofol reduces tissue-Doppler markers of left ventricle function: a transthoracic echocardiographic study
1 Department of Anaesthesiology and Intensive Care
2 Department of Experimental and Clinical Research, Skejby Sygehus, Aarhus University Hospital, DK-8200 Aarhus N, Denmark
* Corresponding author: Department of Anaesthesiology and Intensive Care, and Department of Experimental and Clinical Research, Skejby Sygehus, Aarhus University Hospital, DK-8200 Aarhus N, Denmark. E-mail: jens.rolighed{at}dadlnet.dk
Accepted for publication November 27, 2006.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionAcknowledgementsReferences |
|---|
BACKGROUND: Propofol is thought to minimally depress myocardial function, but mainly to reduce blood pressure by vasodilation. Transthoracic tissue-Doppler echocardiography (TDE) is a novel, validated method of quantifying myocardial function. It provides new insight into myocardial function by measuring myocardial motion. We examined the effects of propofol upon myocardial function by measuring changes in left ventricle function by TDE.
METHODS: We assessed change in myocardial function in propofol anaesthetized ASA I patients tissue tracking displacement (TTD) before anaesthesia onset and repeated measurements after a single propofol bolus dose. Tissue tracking score (TTS), a marker of ejection fraction, was also used (n = 10).
RESULTS: Propofol 1.5–2 mg kg–1 significantly attenuated PSV from 5.64 (1.17) to 4.66 (0.55) cm s–1 (P < 0.0001) and TTD from 10.2 (2.1) to 8.5 (1.4) mm (P = 0.0091), whereas TTP was unchanged [all data: mean (SD)]. TTS declined from 7.2 (1.3) to 6.1 (0.6) mm (P < 0.01). Non-invasive mean blood pressure declined 17% (P < 0.0001).
CONCLUSIONS: The results indicate that myocardial contractile function is compromised concomitantly with reduced cyclic displacement after propofol dosing. Blood pressure declined accordingly. From these results, it is impossible to ascertain whether this was secondary to reduced cardiac filling or a consequence of a direct negative inotropic action of propofol, but it represents a left-shift of the Starling curve. The novel TDE yields new information on myocardial velocities and motion.
Keywords: anaesthesia, general; anaesthetics i.v., propofol; heart, myocardial function; monitoring techniques, transthoracic echocardiography, tissue Doppler
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledgementsReferences |
|---|
Propofol is commonly used in clinical anaesthesia, including in cardiovascular patients. In previous clinical and experimental studies, propofol attenuated diastolic and systolic blood pressures concomitantly with a reduction in vascular resistance, and a decrease in cardiac output in the normal heart.1–6 Propofol dilates blood vessels by inducing NO-synthesis, blocking calcium channels, and activating protein kinase C: all presumed to result in a reduction in left ventricular (LV) preload.7 8 Similar observations have been made in patients with ischaemic myocardium secondary to coronary artery disease.2 This evidence suggests that propofol reduces LV function by reducing preload in both the normal and the dysfunctional heart.5 6Additionally, some reports suggest circulatory failure may originate from the negative inotropic effect of propofol during anaesthesia induction9 10 and it was found in children that Trendelenburg position failed to prevent a decrease in cardiac output after propofol.11 12 We, therefore, strongly advocate the use of clinical markers of myocardial function during induction of anaesthesia.
Echocardiography is a well-established clinical tool that determines cardiac function and pathology. Recently, Doppler-shift technology, already clinically applied in the quantification of fluid dynamics, has become available to quantify tissue motion. In contrast to conventional colour-Doppler flow imaging, tissue-Doppler echocardiography (TDE) data acquisition is filtered to obtain low velocity and high amplitude signals, thereby giving an image of the slower moving myocardium. It provides the examiner with quantitative tissue velocities (e.g. peak systolic velocity, PSV) in the myocardium based on colour-coded Doppler images (Fig. 2). Integrating the myocardial velocity equals myocardial displacement, known as tissue tracking displacement (TTD). TDE variables quantify velocity, direction, and tracking distance in the myocardium and it can be used to characterize LV function.13–17 TDE (both transthoracic and transoesophageal) is increasingly applied in adult echocardiography for evaluating global and regional myocardial function. TDE signal interpretation was facilitated by development of quantification by colour-coded mapping and is proposed as a means to assess LV function.13–17 The MYDISE-study14 revealed that the most consistent TDE measurements are obtained from the basal, septal segment of the LV wall in the apical four-chamber view. The variables displaying highest concordance were PSV, time-to-peak systolic velocity (TTP), and TTD.14 We planned a clinical transthoracic TDE study to test the hypothesis that i.v. propofol alters tissue-Doppler indices associated with LV function. The primary outcome measures were changes in PSV, TTP, and TTD. Secondary outcome measures were changes in blood pressure and heart rate (HR).
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledgementsReferences |
|---|
The study was approved by the local ethics committee, and in agreement with the Helsinki II declaration written informed consent was obtained in each case. Healthy (ASA I) patients scheduled for thoracoscopic sympathectomy for flushing syndrome were asked to participate in the study, and all patients were evaluated for presence of cardiac disease prior to anaesthesia.
Induction
Participants were premedicated with acetaminophen (Pamol retard® NYCOMED, Copenhagen, Denmark) 2 g orally. Monitoring consisted of standard ECG, non-invasive blood pressure, and pulse oximetry. Baseline transthoracic TDE recordings were performed immediately before induction of general anaesthesia. After baseline data acquisition, general anaesthesia was induced with i.v. propofol bolus injection (1.5–2 mg kg–1 over approximately 15 s). No other medications or anaesthetics were given until complete data acquisition was finished. Mask ventilation (45% oxygen) was applied when participants became unresponsive, apnoeic, and had lost their eyelid reflexes. Mask ventilation was discontinued during the repeat TDE recording and recommenced at the conclusion of the investigation with anaesthesia and surgery proceeding.
Transthoracic TDE image acquisition and tissue-Doppler analysis
Participants were studied immediately before anaesthesia induction. Patients were resting in the left lateral decubitus position. Using a Vivid 7® ultrasound platform (GE Healthcare, Horten, Norway) with a 2.5 MHz transducer, TDE data were acquired at sub-maximal end-expiratory breath holding in the awake patient and after sub-maximal end-expiration in the mask ventilated patient. TDE data were acquired from the intercostal apical position (Fig. 1), obtaining the apical four-chamber view, and the transducer was rotated anti-clockwise through 60° to obtain the apical two-chamber view and a further 60° counter-clockwise to obtain the apical long-axis view. Using integrated software for tissue-Doppler imaging with frame rates of > 110 fps, all echocardiograms were performed by one observer (P.T.) and stored digitally for subsequent off-line analysis. Repeat echocardiograms were recorded in the anaesthetized patients immediately after propofol as sole induction agent and before any supplemental medications and intubation.
|
Data images were post-processed using dedicated software (EchoPac®, GE Healthcare, Horten, Norway). PSV, TTP, and TTD were determined with the sampling point cursor placed centrally in the lower third of the basal segment in the interventricular septum (Fig. 2). A tissue tracking score (TTS) was calculated from TTD values using the 16-segment model of LV18 and computing the averaged tracking distance, expressed as single score. All echocardiograms were analysed from taking the mean value of 2–3 artifact-free sinus beats. Two independent observers performed each analysis in a blinded fashion.
|
An example of the on-screen TDE velocity analysis is depicted in Figure 2(A).
Statistical methods
Data variables were tested for normal distribution using the Kolmogorov–Smirnov test. Normally distributed data are expressed as mean (SD). Differences between groups (baseline vs after propofol induction) were compared by two-tailed paired t-test, with patients acting as their own controls. Differences were considered significant if the P-value was <0.05.
Reproducibility and error was tested separately. Intra-observer reproducibility was tested by blinded, repeat analysis of initial PSV data in all 14 participants by one analyst at 3 months after the initial analysis and by performing a regression analysis. Inter-observer variability was tested by correlation coefficient of data from two blinded independent analysts of PSV data in all 14 participants (Figs 3 and 4, respectively).
|
|
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledgementsReferences |
|---|
Fourteen participants (12 f; 2 m) with a median age of 32.5 (range: 26–70) yr were successively enrolled in the study. All participants were unmedicated and had no history of previous cardiac illness. Preoperative cardiac risk assessment, including ECG and chest X-ray, revealed no evidence of manifest cardiac disease.
Transthoracic TDE image acquisition and subsequent analysis was possible in all participants. Full TTS from apical four- and two-chamber views was not possible in four of 14 individuals, mainly due to poor signal/noise ratio in apical segments.
Propofol anaesthesia induction resulted in significant attenuation in blood pressure but no change in HR was observed (Table 1). TDE variables (PSV, TTD, and TTS) declined significantly, whereas TTP was unchanged (Table 1).
|
Evaluation of method agreement (intra- and inter-observer) is depicted in Figures 3 and 4.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledgementsReferences |
|---|
The present study showed significant change in the TDE indices such as PSV, TTD, and TTS. All these parameters declined by 15–22%, indicating a strong attenuation in LV function after induction of anaesthesia with propofol. PSV and TTD/TTS were reduced by a similar order of magnitude as the decline in blood pressure, whereas TTP was not significantly changed. This could with some caution be interpreted as a left-shift of the Frank–Starling pressure–volume relationship curve. These findings are in accordance with previously published results, the attenuation in PSV being paralleled by changes in myocardial tracking dimensions and blood pressures.5 6 Results from these studies indicate that blood pressure reduction depends on vasodilation in both the afterload and preload part of the circulation. Bilotta and colleagues5 disclosed lowered LV preload and reduced afterload as the cause of reduced LV function in a transthoracic echocardiographic study comparing two levels of propofol infusion. The study, however, did not employ the tissue-Doppler method and thus did not enlighten upon myocardial velocities and displacement. Similarly, the comparison between groups in that study did not entail distinguishing the anaesthetized from the awake state, a transition very likely to affect sympathetic discharge.
Fundamentally, attenuation in LV function may be caused by: (i) indirect attenuation of sympathetic discharge by propofol; (ii) alterations in pre- and afterload, or alternatively; (iii) an undisclosed direct negative inotropic effect of propofol upon the myocardium. Previous studies have disclosed that propofol possesses Ca2+-channel blocking properties in addition to inducing endothelial NO release and protein kinase C-activation.7 8 These mechanisms are presumed to lead to vasodilation and hence reduced LV preload (negative Starling effect), whereas effects upon myocardial velocities are only partly accounted for. Several authors have proposed negative inotropic effects from propofol;19 20 however, differences in design, methods, or the influence of concomitant drug administration obscure the basis for comparison with these investigations.
Schmidt and colleagues6 found no change in load-independent LV diameter changes at several levels of propofol sedation using transoesophageal echocardiographic two-dimensional echocardiography with simultaneously recorded invasive pressures. Area-corrected power (PWR/area2) was unchanged, thus, the decline in LV function was, as in the previously discussed study, attributed to load-dependent changes induced by propofol. Our study confirms altered load states, however, as tissue-Doppler technology was also not employed in that study, further comparison is impossible.
The current results show that TTP was unaltered by propofol. TTP could be considered a surrogate marker of the isovolumetric contraction period, which is an afterload-independent index of contractility. It is similar to isovolumic acceleration (IVA), which in an experimental model was unaffected by pre- and afterload changes within a physiologic range.21 Conversely, Andersen and colleagues22 found a significant inverse coupling between IVA and increased preload in a TDE study.
A full TTS was attempted in all 14 patients, but was possible only in 10 patients for technical reasons. In previous studies,14 23 problems were encountered particular in apical segments, where angular, tethering movement, and artifacts produced poor signal-to-noise ratio. This poses a limitation on studies where TTS or apical heart segments are investigated. In general, preference should be given to measurements made from basal segments in the long-axis view. Echocardiographic measurement will always be limited by the acoustic conditions in the individual subject and these can be insurmountable, even to the most experienced echocardiographer. However, obtaining all three apical standard imaging planes is only deemed necessary in patients with regional myocardial dysfunction. All patients in the current study presented a normal preanaesthetic echocardiogram. Additionally, it should be emphasized that the alternative to a reduced number of imaging planes is no visualization at all, and thus having to rely on even more indirect evaluation of myocardial function.
The validity of TDE was previously assessed in numerous studies.14 16 17 23–28 From the MYDISE studies, PSV in the basal segments14 and tissue tracking23 were proved the best tissue-Doppler indices of myocardial function. In the current study, intra- and inter-observer error was estimated to be 8–9%, and thus the TDE method's ability to detect and quantify changes greater than 10% is indirectly confirmed. This does preclude us from making statements about changes of less than this magnitude, however, modifications of <10% in myocardial function rarely have great clinical implications.
Limitations of the current study: As the primary objective was to evaluate LV function by measuring myocardial velocities, no LV area calculations were performed. TTS was attempted in order to form the basis for comparison with currently used methods. As noted, TTS was not possible in some patients; however, the results from 10 patients were conclusive (15.2% drop in ejection fraction) (P = 0.009). Similarly, as the study population consisted of healthy patients undergoing short-duration minor surgery no invasive pressures were coupled with TDE.
Upgrades in the Doppler-processing of TDE permit online assessment with the equipment used in the current study. This could have been most valuable, but will be pending further investigation.
The study used low frame rates (e.g. <250 fps), which is insufficient to allow assumptions about the isovolumic contraction period, which may have enlightened upon PWRmax/area2. Nevertheless, the study demonstrates the simplicity of clinical use of TDE and arriving at similar conclusions as more complicated and less performing setups, which should allow TDE to become more widely clincally employed. The ability to directly assess myocardial velocity and displacement offers great promise in the clinical setting, as this is normal only in experimental investigations, and only indirect measurement through, for example, pulmonary artery catheterization, has been possible. This method is arguably more cumbersome, slower, and only perhaps more accurate. The TDE technique deserves due attention as a most versatile LV function monitor in the future.
|
Acknowledgements |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledgementsReferences |
|---|
This work was supported by the John and Birthe Meyer Foundation, Copenhagen, Denmark, by supplying our departmental research institution with ultrasound equipment.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledgementsReferences |
|---|
1 Paulin M, Jullian-Papouin H, Roquebert PO, Manelli JC. (1987) Hemodynamic effects of propofol used alone for the induction of anesthesia. Ann Fr Anesth Reanim 6:237–9.[Medline]
2 Pinaud M, Lepage JY, Juge C, Helis J, Cozian A. (1987) Effect of propofol on left ventricular function in the coronary patient: combined isotopic and hemodynamic studies. Ann Fr Anesth Reanim 6:243–6.[Medline]
3 Grounds RM, Twigley AJ, Carli F, Whitwam JG, Morgan M. (1985) The hemodynamic effects of intravenous induction. Comparison of the effects of thiopentone and propofol. Anaesthesia 4:735–40.
4 Claeys MA, Gepts E, Camu F. (1988) Haemodynamic changes during anaesthesia induced and maintained with propofol. Br J Anaesth 60:3–9.
5 Bilotta F, Fiorani L, Spinelli F, Rosa G. (2001) Cardiovascular effects of intravenous propofol administered at two infusion rates: a transthoracic echocardiographic study. Anaesthesia 56:266–71.[CrossRef][ISI][Medline]
6 Schmidt C, Roosens C, Struys M, et al. (1999) Contractility in humans after coronary artery surgery. Anesthesiology 91:58–70.[CrossRef][ISI][Medline]
7 Riou B, Besse S, Lecarpentier Y, Viars P. (1992) In vitro effects of propofol on rat myocardium. Anesthesiology 76:609–16.[CrossRef][ISI][Medline]
8 Cook DJ and Housmans PR. (1994) Mechanisms of the negative inotropic effect of propofol isolated ferret ventricular myocardium. Anesthesiology 80:859–71.[CrossRef][ISI][Medline]
9 Tramer MR, Moore RA, McQuay HJ. (1997) Propofol and bradycardia: causation, frequency and severity. Br J Anaesth 78:642–51.
10 Bermudez EA and Chen MH. (2002) Cardiac arrest associated with intravenous propofol during transesophageal echocardiography before DC-cardioversion. Heart Dis 6:355–7.[CrossRef]
11 Bovill JG. (2006) Intravenous anesthesia for the patient with left ventricular dysfunction. Semin Cardiothorac Vasc Anesth 1:43–8.
12 Kardos A, Foldesi C, Nagy A, Saringer A, Kiss A, Kiss G, Marschalko P, Szabo M. (2006) Trendelenburg positioning does not prevent a decrease in cardiac output after induction of anaesthesia with propofol in children. Acta Anaesth Scand 7:869–74.[CrossRef]
13 Sutherland GR, Stewart MJ, Grundstroem KW, et al. (1994) Color Doppler myocardial imaging: a new technique for the assessment of myocardial function. J Am Soc Echocardiogr 7:441–58.[Medline]
14 Fraser AG, Payne N, Madler CF, et al. (2003) Feasibility and reproducibility of off-line tissue Doppler measurement of regional myocardial function during dobutamine stress echocardiography. Eur J Echocardiogr 4:43–53.[CrossRef][Medline]
15 Brodin L. (2004) Tissue Doppler, a fundamental tool for parametric imaging. Clin Physiol Funct Imag 24:147–55.[CrossRef]
16 Vinereanu D, Khokhar A, Tweddel AC, Cinteza M, Fraser AG. (2002) Estimation of global left ventricular function from the velocity of longitudinal shortening. Echocardiography 19:177–86.[CrossRef][ISI][Medline]
17 Voigt JU, Arnold MF, Karlsson M, et al. (2000) Assessment of regional longitudinal myocardial strain rate derived from Doppler myocardial imaging indexes in normal and infarcted myocardium. J Am Soc Echocardiogr 13:588–98.[CrossRef][ISI][Medline]
18 Schiller NB, et al. (1989) Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography committee on standards, subcommittee on quantitation of two-dimensional echocardiograms. (Review). J Am Soc Echocardiogr 2:5358–67.[Medline]
19 Brüssel T, Thiessen J, Vigfusson G, et al. (1989) Haemodynamic and cardiodynamic effects of propofol and etomidate: negative inotropic properties of propofol. Anesth Analg 69:35–40.
20 Vermeyen KM, Erpels FA, Janssen LA, et al. (1987) Propofol-fentanyl anaesthesia for coronary bypass surgery in patients with good left ventricular function. Br J Anaesth 59:1115–20.
21 Vogel M, Cheung MH, Li J, et al. (2003) Noninvasive assessment of left-ventricle force–frequency relationships using tissue Doppler-derived isovolumic acceleration: validation in an animal model. Circulation 107:1647–52.
22 Andersen NH, Terkelsen CJ, Sloth E, Poulsen SH. (2004) Influence of preload alterations on parameters of systolic left ventricular long-axis function: a Doppler tissue study. J Am Soc Echocardiogr 17:941–7.[CrossRef][ISI][Medline]
23 Saha S, Nowak J, Storaa C, et al. (2005) Functional diagnosis of coronary stenosis using tissue tracking provides best sensitivity for left circumflex disease: experience from the MYDISE (myocardial Doppler in stress echocardiography) study. Eur J Echocardiogr 6:54–63.
24 Derumeaux G, Ovize M, Loufoua J, Pontier G, André-Fouet X, Cribier A. (2000) Assessment of non-uniformity of trans-mural velocity by color-coded tissue Doppler imaging. Characterization of normal, ischemic and stunned myocardium. Circulation 101:1390–95.
25 Gorcsan J III, Strum DP, Mandarino WA, Gulati VK, Pinsky MR. (1997) Quantitative assessment of alterations in regional left ventricular contractility with color-coded tissue Doppler echocardiography. Circulation 95:2423–33.
26 Rimbaldi R, Poldermans D, Bax JJ, et al. (2000) Doppler tissue velocity sampling improves diagnostic accuracy during dobutamine stress echocardiography for the assessment of viable myocardium in patients with severe left ventricular dysfunction. Eur Heart J 21:1091–98.
27 Jensen J, Brodin LÅ, Lind B, Eriksson SV, Jensen-Urstad M, Sylvén C. (2001) Deterioration in peak systolic is closely associated to ischaemia during angioplasty: a vector cardiographic and tissue Doppler imaging study. Clin Sci 100:137–43.
28 Cain P, Baglin T, Case C, Spicer D, Short L, Marwick TH. (2001) Application of tissue doppler to interpretation of dobutamine echocardiography and comparison with quantitative coronary angiography. Am J Cardiol 87:525–31.[CrossRef][ISI][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||