|Year : 2022 | Volume
| Issue : 2 | Page : 125-130
Comparison of two doses of intravenous esmolol in attenuation of hemodynamic response to extubation in laparoscopic surgeries
SA Kshama, Laxmi Shenoy, Shweta Sinha
Department of Anaesthesiology, Kasturba Medical College, Manipal, Karnataka, India
|Date of Submission||25-Apr-2022|
|Date of Decision||01-Sep-2022|
|Date of Acceptance||14-Sep-2022|
|Date of Web Publication||29-Oct-2022|
Dr. Shweta Sinha
909, Wing B, Blueberry Woods, Behind Bluedart Courier, Manipal - 576 104, Karnataka
Source of Support: None, Conflict of Interest: None
Aims and Objectives: The purpose of this study was the comparison of hemodynamic variables such as heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure during the extubation period following administration of two doses of intravenous (IV) esmolol.
Materials and Methods: This prospective double-blind randomized controlled trial was conducted on patients (American Society of Anesthesiologists Physical Status), aged between 18 and 65 years, scheduled for elective laparoscopic procedure done under general anesthesia with endotracheal intubation. Sixty participants were randomized into three groups of 20 each, the first two groups received IV esmolol injection of 0.5 mg/kg and 1 mg/kg doses, respectively, and the third group received placebo injection of 10 ml of saline intravenously after the completion of surgery before extubation.
Statistical Analysis: Statistical analysis of data was done using SPSS 20 software. Repeated measures analysis of variance (ANOVA) test was used for the analysis of trends of different parameters within the group. For comparison between the groups and to find if any significant difference exists, one-way ANOVA was used. Post hoc Tukey's test was used to find where the difference originated from, once significant difference was found.
Results: Demographic data were statistically similar between groups. IV administration of esmolol at both 0.5 mg/kg and 1 mg/kg is effective in attenuating heart rate response but IV esmolol bolus of 1 mg/kg is more effective than bolus of 0.5 mg/kg in attenuating blood pressure response to extubation as it provided a more consistent hemodynamic control during the extubation as well as in the postextubation period.
Conclusion: Extubation and emergence from general anesthesia cause significant increases in heart rate and blood pressure and emphasis must be given on attenuation of this sympathetic response, especially in vulnerable patients. IV administration of esmolol is effective in attenuation of heart rate response and blood pressure response with consistently good hemodynamic control during extubation postoperatively.
Keywords: Attenuation, control stress response, esmolol, extubation, hemodynamic response
|How to cite this article:|
Kshama S A, Shenoy L, Sinha S. Comparison of two doses of intravenous esmolol in attenuation of hemodynamic response to extubation in laparoscopic surgeries. Indian Anaesth Forum 2022;23:125-30
|How to cite this URL:|
Kshama S A, Shenoy L, Sinha S. Comparison of two doses of intravenous esmolol in attenuation of hemodynamic response to extubation in laparoscopic surgeries. Indian Anaesth Forum [serial online] 2022 [cited 2023 Jan 30];23:125-30. Available from: http://www.theiaforum.org/text.asp?2022/23/2/125/359856
| Introduction|| |
Hypertension and tachycardia are well-documented events during extubation. These responses could be catastrophic and can lead to complications such as myocardial ischemia, heart failure, cerebrovascular hemorrhage, and pulmonary edema, more so in patients who are hypertensive. Hence, it is of paramount importance to attenuate these hemodynamic responses during extubation. These hemodynamic responses reflect sympathoadrenal reflex stimulation (epipharyngeal and laryngopharyngeal stimulation) with a concomitant increase in plasma level of catecholamine and activation of alpha- and beta-adrenergic receptors. The development of postoperative hypertension warrants immediate assessment and treatment to reduce the risks of myocardial infarction, arrhythmias, congestive heart failure, stroke, bleeding, and other end-organ damage.,
The response may be attenuated by pharmacological interventions including esmolol (0.51 mg/kg intravenous [IV] 2–5 min before extubation), glyceryl trinitrate, magnesium, propofol infusion, remifentanil/alfentanil infusions, IV lidocaine (1.5 mg/kg over 2 min), topical lidocaine 10%, and perioperative oral nimodipine with labetalol.,
Several studies suggest that beta-blockers reduce perioperative myocardial ischemia and may decrease the risk of perioperative myocardial infarction and cardiovascular death in high-risk patients.,,, β blockers are widely used agents for attenuating or treating hemodynamic responses in the perioperative period. Esmolol is a short-acting β1-selective adrenergic receptor antagonist with a rapid onset. These characteristics make esmolol a useful drug for preventing and controlling sympathetic responses that occur due to noxious stimuli, such as tracheal extubation. Esmolol is given to attenuate hemodynamic response to extubation and their adverse effects will facilitate more wider and frequent use of esmolol during extubation. This will help to lessen adverse outcomes during extubation and provide safe emergence under general anesthesia.
To compare the hemodynamic effects of IV administered esmolol in two doses 0.5 mg/kg and 1 mg/kg, in attenuating hemodynamic responses to tracheal extubation and emergence from general anesthesia in patients who have undergone laparoscopic surgeries.
The objective of this study was to the comparison of hemodynamic variables during the extubation period following the administration of two doses of IV esmolol.
The objective of this study was to observe any adverse effects following the administration of the drug and treat them and assess the quality of extubation using the Eshak four-point scale.
| Materials and Methods|| |
This prospective, double-blind, randomized controlled trial was conducted at the Department of Anaesthesiology, Kasturba Medical College, Manipal, after approval from Departmental Dissertation and Institutional Ethics Committee (IEC – 916/2018). Then, the trial was registered prospectively at the Clinical Trials Registry, India (registration number CTRI/2019/07/020151). The study period was between July 2019 and November 2020. After written and informed consent, 60 American Society of Anesthesiologists Physical Status of either gender, posted for laparoscopic surgery under general anesthesia was enrolled in the study.
Patients not giving consent, suspected allergy to study drugs (esmolol), difficult airway, history of bronchial asthma or cardiovascular diseases, and patients on β-blockers were excluded from the study.
Based on the clinically important difference of 5 set by the investigation and a standard deviation of 5 – both the values derived from the pilot study; a sample size of 15.68 rounded off to 20 to account for attrition in each group and a total sample size of 60 were calculated using a formula based on comparison of means between the groups with 80% power and 95% level of significance. Based on the comparison of the mean between the two groups, the formula for sample size calculation as per the pilot study with 10 patients in each group was.
n = 2([zα] + z [1-β])2 σ2/d2
Z = 1.96
α =0.05 (i.e. 95% level of significance), β =0.2 (i.e. 80% power)
σ = standard deviation, σ2 = variance
d = clinically important difference set by the investigator, σ and d based on the pilot study is 5
n = number in each group
Now putting the abovementioned values, n = 15.68 accounting for attrition, n = 20 in each group.
Randomization was done using a computer-generated randomization table and patients (blinded) were allocated to one of the three groups. Randomization was done by a consultant anesthesiologist (not involved in data collection), who prepared the drug in a syringe (different doses of esmolol or saline) and provided it to the concerned anesthesiologist (operator), concealed in an opaque envelope on the day of surgery.
Group 0.5–0.5 mg/kg of esmolol (in a 10 ml syringe, diluted with saline to a volume of 10 ml) was administered to patients in this group IV after the completion of surgery postreturn of spontaneous breathing efforts, at MAC (minimum alveolar concentration) value of less than or equal to 0.3, when train of four count was 3 or >3.
Group 1–1 mg/kg of esmolol (in a 10 ml syringe, diluted with saline to a volume of 10 ml) was administered to patients in this group IV after the completion of surgery postreturn of spontaneous breathing efforts, at MAC value of ≥0.3, when train of four count was 3 or >3.
Group C – Patients in the control group were administered 10 ml saline intravenously after the completion of surgery postreturn of spontaneous breathing efforts, at MAC value of ≥ 0.3, when train of four count was 3 or >3.
All the patients underwent a detailed preanesthetic evaluation a day before surgery. On the day of surgery after shifting the patient to the operation theater, standard monitors were attached and baseline vitals were recorded. IV access was established.
After preoxygenation for 3 min, the conduct of general anesthesia was done as per institution protocol with neuromuscular blockade and endotracheal intubation. On completion of surgery, inhalational anesthetics were tapered and cut off. Once MAC of 0.3 was reached, train of four ratio was examined by a peripheral nerve stimulator. When train of four ratio was 3 and above and postreturn of spontaneous breathing, residual neuromuscular blockade was reversed with IV neostigmine of 0.05 mg/kg and glycopyrrolate of 0.01 mg/kg. The study drug was administered after reversal. The patient was extubated once he/she started to obey verbal commands and started to take tidal volume breaths of at least 6 mL/kg body weight.
Hemodynamic variables such as heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure were recorded before administration of the study drug, postadministration, just before extubation, then for every single minute for the first 5 min postextubation and finally at 10 min after extubation.
Adverse events if any and treatment received were recorded. Bradycardia (heart rate [HR] <50/min) was proposed to be treated with IV atropine (0.6 mg). Hypotension (MAP <20% of baseline or systolic blood pressure SBP <90 mmHg) was planned to be treated with 200 ml of crystalloid boluses or IV mephentermine 3 mg in incremental boluses.
Data analysis was done using Statistical Package for the Social Sciences (SPSS 20 software, IBM India Private Limited, Bangalore, India). Data were analyzed for the presence of normality using Shapiro–Wilk's test. Demographic data such as age, weight, height, and body mass index were analyzed by one-way analysis of variance (ANOVA) test (Normal distribution), whereas gender was analyzed using the Kruskal–Wallis test (skewed distribution). Repeated measures ANOVA were used for the analysis of trends of hemodynamic profile within the group (Normal distribution). Since the study involved three different groups with different sets of participants, for comparison between the groups and to find if any significant difference exists, one-way ANOVA was used. Once a significant difference was found, post hoc Tukey's test was used to find where the difference originated from.
| Results|| |
Demographic data were found to be comparable between groups [Table 1].
The mean values of HR at different time points in the extubation period of all three groups with corresponding standard deviations are compared [Table 2]. The baseline HR was comparable but statistically significant differences were found from immediately after drug administration till 5 min postextubation. Intergroup comparison was done between the three groups, statistically significant lowering of HR compared to control was found in both the group of patients immediately after drug administration till 5th min postextubation. There was no statistically significant difference found between Group 0.5 and Group 1.
Statistically significant results were found from immediately after drug administration till 10th min postextubation when the mean value with corresponding standard deviation of SBP at different time points in the extubation period of all three groups was compared [Table 3]. When intergroup comparisons were made, statistically significant decrease in SBP was found in Group 0.5 compared to Group C immediately after drug administration, 2nd, 3rd, 4th, and 5th mine postextubation, whereas with Group 1, statistically significant results were found consistently in almost all time points. With Group 0.5 and Group 1, statistically significant difference was found only at the 1st min and 2nd min postextubation.
|Table 3: Comparison of systolic blood pressure at different time intervals|
Click here to view
The mean values of DBP at different time points in the extubation period of all three groups with corresponding standard deviations are compared [Table 4]. Statistically significant results were found from just before extubation till the 5th min postextubation. When intergroup comparisons were made, statistically significant decrease in DBP was found in Group 0.5 compared to Group C at 3rd and 4th min postextubation, whereas with Group 1, statistically significant results were found consistently in almost all time points. In Group 0.5 and Group 1, statistically significant difference was found only at just before extubation and at 1st min postextubation.
|Table 4: Comparison of mean diastolic blood pressure at different time intervals|
Click here to view
The mean values of mean arterial blood pressure at different time points during the extubation period of all three groups with corresponding standard deviations [Table 5]. Statistically significant results were found from immediately after extubation till the 5th min postextubation. When intergroup comparisons were made, statistically significant decrease in mean arterial blood pressure was found inconsistently in Group 0.5 compared to Group C at immediately before extubation, 3rd, 4th, and 5th min postextubation. Between Group 1 and Group C, statistically significant decreases in mean arterial pressures were found consistent at almost all time points. Between Group 0.5 and Group 1, statistically significant difference was found only at just before extubation and at 1st min and 2nd min postextubation.
|Table 5: Comparison of mean arterial pressure at different time intervals|
Click here to view
There were no adverse effects seen in any of the study groups.
The quality of extubation was assessed using Eshak's four-point scale and analyzed using the Chi-square test. With a P of 0.709, it was found to be comparable between groups, hence the administration of IV esmolol in either of the doses did not affect the quality of extubation [Table 6].
| Discussion|| |
This study focused on the endotracheal extubation response and its pharmacological attenuation. Complications after tracheal extubation are three times more common than complications occurring during tracheal intubation and induction of anesthesia. Extubation is often associated with hemodynamic responses and this can be attenuated pharmacologically. In our study, we used esmolol IV in two different doses to attenuate the extubation response and the effects of these different doses of esmolol were compared.
Few studies favor the use of IV esmolol in attenuating hemodynamic responses which could prevent adverse intraoperative events such as myocardial infarction and stroke and can produce favorable outcomes are.
Alkaya et al. in 2014 evaluated the effect of IV infusion of esmolol was used to prevent and control the hemodynamic response during extubation after elective craniotomy. In patients who received esmolol, hemodynamic parameters were lower after esmolol infusion compared to the control group postextubation. Thus, it was inferred that infusion of 2 mg/kg esmolol before extubation can attenuate hypertensive and tachycardic responses during extubation postelective craniotomy. In our study, we used boluses, which were equally effective in blunting sympathetic response without any significant hypotension.
Nagrale et al. conducted a study on 90 patients to evaluate hemodynamic effects of IV propofol, lignocaine, and esmolol given 2 min before extubation. It was concluded that IV esmolol is preferred for attenuation of hemodynamic responses when compared with IV propofol and IV lignocaine.
Tendulkar and Ninave in 2017 did a randomized control trial (RCT) to compare the effect of IV dexmedetomidine to that of esmolol in preventing the hemodynamic response to the emergence and tracheal extubation. Patients in the esmolol group were administered IV esmolol bolus of 1.5 mg/kg 2 min before extubation. Similarly, patients in the second group received IV dexmedetomidine bolus of 0.5 mcg/kg over 10 min before extubation. Thus, it was concluded that both IV esmolol and dexmedetomidine blunt the hemodynamic response effectively, but IV dexmedetomidine was associated with higher sedation scores.
Ollila et al. in 2019 conducted a review on the usage of IV esmolol for cardiac protection in the perioperative period. The review involved 196 adult patients from three randomized control trials, it was concluded that administration of IV esmolol was a good choice for the avoidance of myocardial ischemic changes in the perioperative period.
Prajwal Patel et al. conducted a study where 60 patients scheduled for elective surgical procedures were randomly allocated into two groups of 30 each. Group I – esmolol 1.5 mg/kg and Group II – labetalol 0.25 mg/kg were administered 2 min before extubation after following a standard perioperative anesthetic management. Hemodynamic parameters recorded include HR, SBP, DBP, and MAP at baseline, reversal, study drug, 1 min after study drug, extubation, and at 1-, 2-, 3-, 4-, 5-, and 15-min postextubation. Esmolol was more efficient than labetalol at extubation and immediately postextubation for attenuating hemodynamic response.
In this study, we used esmolol intravenously in two doses of 0.5 and 1 mg/kg. We found that although both doses attenuate tachycardia, esmolol given at 1 mg/kg is more effective to attenuate blood pressure response to extubation. In the control group, we found increase in the SBP compared to baseline during extubation. Although patients who received 0.5 mg/kg of IV esmolol had decrease in SBP but at crucial time points such as just before extubation and 1 min following extubation and SBP remained elevated. Patients who received 1 mg/kg of the drug had persistent decrease in SBP at all-time points after drug administration. There was no incidence of exaggerated hypotension (30%) in both groups. We also found significant tachycardia in the control group when compared to the other groups up to 10 min.
There were a few limitations in this study:
- Patients who were already hypertensive, who would benefit from the prevention of increase in blood pressure during extubation were not included
- Only laparoscopic surgeries were included
- It was a single-center trial hence might not reflect the actual population.
| Conclusion|| |
Extubation and emergence from general anesthesia cause significant increase in HR and blood pressure and emphasis must be given on their attenuation, especially in vulnerable patients.
IV administration of esmolol at both 0.5 mg/kg and 1 mg/kg is effective in attenuating HR response but IV esmolol bolus of 1 mg/kg is more effective than bolus of 0.5 mg/kg in attenuating blood pressure response to extubation as it provided a more consistent hemodynamic control during the extubation as well as postextubation period.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
O'Dwyer JP, Yorukoglu D, Harris MN. The use of esmolol to attenuate the haemodynamic response when extubating patients following cardiac surgery – A double-blind controlled study. Eur Heart J 1993;14:701-4.
Lowrie A, Johnston PL, Fell D, Robinson SL. Cardiovascular and plasma catecholamine responses at tracheal extubation. Br J Anaesth 1992;68:261-3.
Coriat P, Mundler O, Bousseau D, Fauchet M, Rous AC, Echter E, et al.
Response of left ventricular ejection fraction to recovery from general anesthesia: Measurement by gated radionuclide angiography. Anesth Analg 1986;65:593-600.
Prys-Roberts C, Greene LT, Meloche R, Foëx P. Studies of anaesthesia in relation to hypertension. II. Haemodynamic consequences of induction and endotracheal intubation. Br J Anaesth 1971;43:531-47.
Miller KA, Harkin CP, Bailey PL. Postoperative tracheal extubation. Anesth Analg 1995;80:149-72.
Olympio MA, Youngblood BL, James RL. Emergence from anesthesia in the prone versus supine position in patients undergoing lumbar surgery. Anesthesiology 2000;93:959-63.
Raby KE, Brull SJ, Timimi F, Akhtar S, Rosenbaum S, Naimi C, et al.
The effect of heart rate control on myocardial ischemia among high-risk patients after vascular surgery. Anesth Analg 1999;88:477-82.
London MJ, Hur K, Schwartz GG, Henderson WG. Association of perioperative β-blockade with mortality and cardiovascular morbidity following major noncardiac surgery. JAMA 2013;309:1704-13.
Welten GM, Chonchol M, Hoeks SE, Schouten O, Bax JJ, Dunkelgrün M, et al.
Beta-blockers improve outcomes in kidney disease patients having noncardiac vascular surgery. Kidney Int 2007;72:1527-34.
Feringa HH, Bax JJ, Schouten O, Kertai MD, van de Ven LL, Hoeks S, et al.
Beta-blockers improve in-hospital and long-term survival in patients with severe left ventricular dysfunction undergoing major vascular surgery. Eur J Vasc Endovasc Surg 2006;31:351-8.
Alkaya MA, Saraçoğlu KT, Pehlivan G, Eti Z, Göğüş FY. Effects of esmolol on the prevention of haemodynamic responses to tracheal extubation after craniotomy operations. Turk J Anaesthesiol Reanim 2014;42:86-90.
Nagrale MH, Indurkar PS, Pardhi CS. Comparative study on haemodynamic response to extubation: Attenuation with lignocaine, esmolol, propofol. Int J Res Med Sci 2016;4:144-51.
Tendulkar MP, Ninave SS. Prospective comparison of pressor and airway responses to intravenous esmolol and intravenous dexmedetomidine during emergence from general anaesthesia and extubation. J Kris Inst Med Sci Univ 2017;6:49-56.
Ollila A, Vikatmaa L, Sund R, Pettilä V, Wilkman E. Efficacy and safety of intravenous esmolol for cardiac protection in non-cardiac surgery. A systematic review and meta-analysis. Ann Med 2019;51:17-27.
Prajwal Patel HS, Shashank MR, Shivaramu BT. Attenuation of hemodynamic response to tracheal extubation: A comparative study between esmolol and labetalol. Anesth Essays Res 2018;12:180-5.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]