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| Year : 2010
| Volume
: 13 | Issue : 3 | Page
: 217-223 |
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| A randomized trial of anesthetic induction agents in patients with coronary artery disease and left ventricular dysfunction |
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Raveen Singh, Minati Choudhury, Poonam Malhotra Kapoor, Usha Kiran
Department of Cardiac Anesthesia, All India Institute of Medical Sciences, New Delhi - 110 028, India
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| Date of Submission | 16-Nov-2009 |
| Date of Acceptance | 06-Apr-2010 |
| Date of Web Publication | 6-Sep-2010 |
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 Abstract | | |
The deleterious effects of anesthetic agents in patients suffering from coronary artery disease are well known. The risk increases when a patient has compromised ventricular function. There is a paucity of literature regarding the choice of the suitable agent to avoid deleterious effects in such patients. The use of etomidate and propofol has been considered superior to other intravenous anesthetic agents in these groups of patients. The aim of the present study is to compare the hemodynamic effects of anesthesia induction with etomidate, thiopentone, propofol, and midazolam in patients with coronary artery disease and left ventricular dysfunction. This randomized clinical trail was conducted at the All Indian Institute of Medical Sciences, New Delhi, India. Sixty patients with coronary artery disease and left ventricular dysfunction (ejection fraction < 45%) scheduled for elective coronary artery bypass surgery participated in this study. After stabilization baseline hemodynamic data stroke volume variation and systemic vascular resistance index were recorded for all patients (Flo Trac TM sensor with Vigileo cardiac output monitor used for hemodynamic monitoring). The patients were randomly alloted to one of the four groups and the intravenous induction agent was administered for over 60 - 90 seconds (Group E - Etomidate 0.2 mg/Kg; Group M - Midazolam 0.15 mg/Kg; Group T - Thiopentone 5 mg/Kg; Group P - Propofol 1.5 mg/Kg). Hemodynamic data were recorded at one minute intervals starting from induction till seven minutes after intubation, - the end point of the present study. There was a significant decrease in the heart rate in comparison to the baseline(-7 to -15%, P = 0.001), mean arterial pressure (-27 to -32%, P = 0.001), cardiac index (-36 to -38%, P = 0.001), and stroke volume index (-27 to -34%, P = 0.001) after induction in all four groups. The hemodynamic response was similar in all the four groups. There was no significant change in central venous pressure and stroke volume variation (SVV) during induction and intubation, while the effects on the systemic vascular resistance index (SVRI) were variable. The midazolam group was the most effective in preventing intubation stress (tachycardia,hypertension). The change from baseline values in heart rate (+ 4%, P = 0.12) and mean arterial pressure (-1%, P = 0.77) after intubation were not statistically significant in the midazolam group. The etomidate group was the least effective of all the four groups in minimizing stress response, with statistically significant increase from baseline in both heart rate (P = 0.001) and mean arterial pressure (P = 0.001) at 1 minute after intubation. All the four anesthetic agents were acceptable for induction in patients with coronary artery disease and left ventricular dysfunction despite a 30 - 40% decrease in the cardiac index. Clinician experience along with knowledge of the potential interactions (e.g., premedication, concurrent opioid use) is needed to determine hemodynamic stability during anesthetic induction in these patients with ventricular dysfunction. Keywords: Anesthetic induction agents, coronary artery disease, left ventricular dysfunction
How to cite this article:
Singh R, Choudhury M, Kapoor PM, Kiran U. A randomized trial of anesthetic induction agents in patients with coronary artery disease and left ventricular dysfunction. Ann Card Anaesth 2010;13:217-23 |
How to cite this URL:
Singh R, Choudhury M, Kapoor PM, Kiran U. A randomized trial of anesthetic induction agents in patients with coronary artery disease and left ventricular dysfunction. Ann Card Anaesth [serial online] 2010 [cited 2022 Aug 12];13:217-23. Available from: https://www.annals.in/text.asp?2010/13/3/217/69057 |
| Introduction | |  |
Anesthetic induction techniques for cardiovascular surgery are usually based on considerations such as hemodynamic stability, effects on myocardial oxygen supply, and demand and minimizing intubation stress response. [1],[2] A wide variety of induction agents, such as, thiopentone, etomidate, propofol, midazolam, and ketamine have been used for anesthetizing patients with cardiac disease.
Patients with coronary artery disease (CAD) and left ventricular dysfunction presenting for coronary artery bypass grafting (CABG) represent a high-risk group among the cardiac surgical population. Various authors have expressed concerns regarding induction of anesthesia with agents such as thiopentone, propofol, and ketamine. [3],[4],[5] Use of etomidate is advocated in patients with compromised cardiopulmonary function, because of its minimal cardiovascular and respiratory depressant effects. It is also beneficial because of lack of histamine release. Various studies in patients with good ventricular function have demonstrated the stable cardiovascular profile of etomidate in cardiac patients, while others have shown stable hemodynamics with midazolam, thiopentone, and propofol. [6],[7],[8],[9]
| Materials and Methods | | |
After approval from the institutional ethics committee and written informed consent from the patients, this study was conducted on 60 patients with coronary artery disease and left ventricular dysfunction (ejection fraction < 45%), scheduled for elective CABG surgery.
Patients with associated valvular heart disease, persistent arrhythmias, congestive cardiac failure, on mechanical ventilation, IABP, emergency surgery, known adrenal insufficiency, history of steroid use in the preceding six months, and those with severe systemic non-cardiac disease, other than diabetes and hypertension, were excluded from the study. The patients were randomized into one of the four groups by the sealed envelope technique, depending on the anesthetic induction agent (Group E - Etomidate 0.2 mg/Kg, Group M - Midazolam 0.15 mg/Kg, Group T - Thiopentone 5 mg/Kg, and Group P - Propofol 1.5 mg/Kg).
All preoperative cardiac medications were continued till the morning of the surgery, except angiotensin converting enzyme inhibitors. All the patients received oral diazepam 10 mg on the night before surgery and intramuscular morphine of 0.2 mg/Kg with promethazine 25 mg one hour before anesthesia induction as per institutional protocol.
Initial monitoring inside the operation theater included five lead electrocardiograms, non-invasive blood pressure, and pulse oximetry. Under local anesthesia an arterial line was placed in the right radial artery and central venous line in the right internal jugular vein. The Flo Trac TM sensor with Vigileo cardiac output monitor (Edwards Life Sciences, Irvine, USA) was connected to the radial arterial cannula. The FloTrac - Vigileo monitor is a relatively novel device to measure cardiac output, based on the analysis of the arterial pressure waveform. The processing unit applied a proprietary algorithm to the digitalized pressure wave, in conjunction with the patient's demographic data entered, to yield cardiac output (CO), cardiac index (CI), stroke volume (SV), stroke volume index (SVI), and stroke volume variation (SVV). If the central venous pressure (CVP) was entered (or analog recording from cardiac monitor slaved), the device derived the systemic vascular resistance (SVR) and systemic vascular resistance index (SVRI).
Intravenous fentanyl 4 mcg/Kg was then administered over a period of one minute to all patients. After a period of five minutes, the baseline data in the form of heart rate, systolic, diastolic, and mean systemic arterial pressures, CVP, CO, CI, SV, SVI, SVV, SVR, and SVRI were recorded during the study period in all the patients. Ssubsequently, general anesthesia was induced with one of the agents, depending on the group.
The induction agent was administered in small doses over a period of 60 - 90 seconds and loss of eyelash reflex and lack of response to verbal command was documented. Vecuronium bromide 0.1 mg/Kg was administered to facilitate tracheal intubation, which was done three minutes after the end of induction. The stress response to laryngoscopy and tracheal intubation is secondary to marked increase in sympathetic activity and manifested in general as tachycardia and hypertension. Hemodynamic changes; 20beats/minute or 20 mmHg difference in heart rate and blood pressure respectively were considered to be significant. The patients were ventilated by mask and ventilator till intubation as manual ventilation might lead to development of exposed to PEEP which might cause the changes in hemodynamics. Hemodynamic data was recorded at one minute intervals starting from induction till seven minutes after intubation, the end point of the present study. Throughout this period the lungs were mechanically ventilated with 50% air-oxygen mixture, to maintain an end-tidal carbon dioxide between 35 and 40 mmHg.
Stastical analysis
Patient characteristics and hemodynamic variables are expressed as a mean (standard deviation). Data were analyzed using the SPSS software (SPSS version 15; SPSS, Chicago, IL). Pair wise analysis of hemodynamic data at one minute intervals in each group was done using a two-way ANOVA test followed by post-hoc analysis using Fisher's Least Significant Difference (LSD) method (time trend). Comparison between the four groups of patients was conducted by using the one-way ANOVA followed by post hoc analysis using the Bonferroni method. Pearson's correlation coefficient was used to analyze the relationship between baseline CVP and left ventricular dysfunction. In all the comparisons a P value of < 0.05 was considered to be significant. A power analysis from previous studies revealed a sample size of 15 patients per group was required to achieve a power of 80% and an a 0.05 for detection of the desired hemodynamic changes(20beats/minute or 20 mmHg difference in heart rate and blood pressure respectively).
| Results | | |
The four groups were homogenous with regard to demographic variables, ejection fraction, preoperative drug therapy; and prevalence of diabetes mellitus and hypertension [Table 1]. All patients had moderate left ventricular dysfunction with ejection fraction ranging between 30 and 45%.
Baseline hemodynamic variables were comparable between the four groups [Table 2] and [Table 3]. There was a significant decrease from the baseline in the heart rate (P = 0.001 in each group), mean arterial pressure (P = 0.001 in each group), CI (P = 0.001 in each group), and SVI (P = 0.001 in each group) after induction, in all four groups of patients and these variables increased above baseline one minute after intubation [Table 2]. However, intergroup comparison revealed no changes in these variables during this period [Table 2]. The thiopentone group recorded the least decrease in heart rate (-7%), while the maximum decrease was seen in the midazolam group (-15%) [Figure 1]. There was a significant decrease in the stroke volume index (-27 to -34%) and decrease in CI (-36 to -38%) [Figure 1]. The decrease in mean arterial pressure ranged from -27 to -32% and was similar across the four groups (P = 0.69) [Figure 2]. This was accompanied by variable changes in SVRI [Figure 2].  | Table 2: Hemodynamic variables in the four groups at different time points
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 | Table 3: Hemodynamic variables in the four groups at different time points
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 | Figure 1: The maximum percentage change from baseline in heart rate, stroke volume index and cardiac index after induction and after intubation
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 | Figure 2: The maximum percentage change from baseline in mean systemic arterial pressures and systemic vascular resistance index after induction and after intubation
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Midazolam was most effective in preventing intubation stress. The change from baseline values in heart rate (+4%, P = 0.12) and mean arterial pressure (-1%, P = 0.77) after intubation was not statistically significant [Table 2] and [Figure 2]. Etomidate was the least effective in minimizing the stress response, with a statistically significant increase from baseline in both heart rate (P = 0.001) and mean arterial pressure (P = 0.001), one minute after intubation [Table 2].
Intragroup comparison revealed that there was no significant change in CVP and SVV during induction and intubation, while the effects on SVRI were variable (P = 0.05 in each case, [Table 3]). Baseline CVP value ranged from 3 to 15 mmHg with wide variation and did not correlate with the degree of ventricular dysfunction (r = +0.10, P = 0.46). The time trends of hemodynamic variables over time for all four groups are shown in [Table 2] and [Table 3].
Myoclonus was observed in two patients in the etomidate group, while one patient in the propofol group required active volume resuscitation as the CI decreased below 1.8 L/min/m 2 after induction.
| Discussion | | |
Induction of general anesthesia may be a critical period during CABG surgery, specially in presence of LV dysfunction. A wide variety of anesthetic drugs are available and some are marketed (e.g., etomidate) to be especially safe in cardiac patients. The present study demonstrates that a wide variety of intravenous induction techniques (Etomidate, thiopentone, midazolam, propofol) may be safely used for anesthetizing high-risk patients undergoing CABG. The present study was designed to mimic the clinical practice rather than to study each drug as the sole anesthetic (which is rarely done in practice). Concurrent opioid use (fentanyl 4 μ/kg) could have influenced hemodynamics, but such small doses have been shown to produce minimal cardiovascular changes. [3]
The hemodynamic changes brought about by anesthesia induction in our study essentially consisted of a moderate decrease in CO, may have been caused by decrease in SV, accompanied by a decrease in arterial pressure. Anesthesia may be associated with depression of sympathetic activity; this is required for maintenance of hemodynamics in patients with poor ventricular function. A comparable decrease in hemodynamics was observed in all four groups in our study, which can be explained by the hypothesis that most of the hemodynamic changes are attributable to the loss of sympathetic stimulation on induction rather than to anesthetic drugs per se. [10] Reiz et al. studied the effects of thiopentone on the cardiac performance of eight patients with stable CAD and normal ventricular function. [8] Thiopentone in a dose of 6 mg/kg (given over two minutes) decreased arterial blood pressure (27%), SVR (20%), and SVI (18%), while the heart rate increased (10%). Associated with these hemodynamic changes they also demonstrated a decrease in myocardial oxygen consumption (MVO 2 fell 39%), which was beneficial to the patients. Their patients were not premedicated and none of them received concurrent opioids, which could have accounted for the slightly greater decrease in our thiopentone group. Concerns regarding the use of thiopentone in CAD patients originated from studies that had shown increase in heart rate and increase in myocardial oxygen uptake with thiopentone. [11] Reiz et al., however, postulated that this hemodynamic effect was probably related to a different administration technique -thiopentone 4 mg/kg was administered over 30 seconds
Massaut et al. studied the hemodynamic effects of midazolam in eight patients with CAD. [7] They reported a decrease in heart rate (9%), mean arterial pressure (17%), CI (9%), and SVR (12%). Their study was conducted in anesthetized patients, which could account for the smaller changes in hemodynamics in their study, as compared to ours. The authors started the hemodynamic study after achieving stable conditions after induction. They also demonstrated the beneficial effects on endocardial viability and advocated the use of midazolam as a supplement to fentanyl anesthesia in patients CAD.
Tarnow et al. used midazolam 0.2 mg/kg in premedicated patients with CAD (normal ventricular function) along with fentanyl 5 μ/kg and demonstrated a 20% decrease in CI, SVI, and mean arterial pressure (MAP). [12] There were no significant changes in heart rate, CVP or SVR. These changes were similar to our results. The slightly lower decrease in CI and MAP could be attributed to the slow administration of drugs separately, over a period of eight minutes, in their study.
Stephan et al. studied the effects of propofol in 12 patients scheduled for CABG. The patients were premedicated and received propofol 2 mg/kg intravenously followed by an infusion of the same drug (200 μ/kg/min). Hemodynamic variables recorded 30 minutes later showed almost a 20 - 25% decrease in Mean arterial pressure (MAP), CI, and SVI. [9] Their results were similar to our propofol group, which had a slightly larger decrease due to associated opioid administration and left ventricular dysfunction. Various other studies have also demonstrated a decrease in blood pressure ranging from 20 to 30% with use of propofol in CAD patients. [13] .Some authors have especially advocated a combination of propofol with an opioid as a popular technique for intravenous anesthesia in patients with ventricular dysfunction. [14] They have, however, suggested that a dose of propofol should be reduced and the drug administered slowly. This is important as one of our patients did show significant decrease in cardiac index requiring volume resuscitation (this patient was on preoperative ACE inhibitors).
Lischke et al. evaluated the ST segment changes after induction with etomidate, propofol, and midazolam in 60 patients undergoing CABG. [15] Four patients in the propofol group had ST changes prior to induction and these changes disappeared in two patients after induction. In patients who received midazolam, the pre-existing ST changes remained unchanged during the post-induction period. In the etomidate group also there were three patients with prior ST changes that remained unchanged, but one other patient developed ST segment deviation after induction. They explained that propofol, while reducing coronary perfusion, also decreased myocardial oxygen consumption.
The new lipuro emulsion preparation of etomidate has decreased the incidence of some adverse effects like pain, phlebitis, and myoclonus. The apprehension regarding its adrenal suppressive action has also been ill-founded, as most recent studies have demonstrated only a transient decrease in serum cortisol levels after a single induction dose of etomidate, which is not clinically significant. [16]
Some workers have also used ketamine (in combination with benzodiazepines) for patients with CAD and demonstrated stable hemodynamics, although there is a potential risk of increased myocardial oxygen demand. [17],[18]
No potential or actual benefit of the anesthetic technique exists without some cost disadvantage. The higher depressive action of a drug may be beneficial in preventing the intubation response (e.g., midazolam), while a lesser depressive drug (e.g., etomidate) may fail to block the intubation response. The hemodynamic effects of anesthetic induction agents in cardiac patients depend to a great extent, on the technique, skill, and experience of drug administration by the clinician (e.g., slow infusion vs. rapid bolus). Dose adjustment and speed of induction are probably more important than which individual drugs are used.
Limitations of the study
Most of our patients had a decrease in blood pressure and CI ranging from 30 - 40%. This can be detrimental in some patients who are on the limits of their reserve. The authors speculated that a slower induction spread over two to four minutes may have probably resulted in lesser hemodynamic derangement.
There were no visible ST segment changes in any of our patients and we did not do a formal analysis of ST segment changes in the four different groups.
| Conclusions | | |
Etomidate, midazolam, thiopentone, and propofol may all be used while anesthetizing patients with CAD and left ventricular dysfunction. The outcome of anesthetic induction may depend on factors such as the speed of injection, route, dose and experience of the clinician, other than the property of the agent itself.
| Acknowledgments | | |
The authors are thankful to MV Kalaivani, Scientist, Department of Biostastistic, AIIMS, for her extensive help in the statistical analysis of the study.
| References | | |
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Correspondence Address:
Minati Choudhury
Department of Cardiac Anesthesia, 7th Floor, C N Center, All India Institute of Medical Sciences, New Delhi
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0971-9784.69057
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3] |
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