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ORIGINAL ARTICLE
Year : 2010  |  Volume : 4  |  Issue : 3  |  Page : 163-168

Comparison of esmolol and labetalol, in low doses, for attenuation of sympathomimetic response to laryngoscopy and intubation


Department of Anaesthesia, J N Medical College, Aligarh, India

Correspondence Address:
Sarvesh P Singh
112, Doctors Hostel, J P N A Trauma Centre, AIIMS, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1658-354X.71573

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Date of Web Publication12-Oct-2010
 

  Abstract 

Objective: The present study compared the efficacy of esmolol and labetalol, in low doses, for attenuation of sympathomimetic response to laryngoscopy and intubation. Design: Prospective, randomized, placebo controlled, double-blinded study. Setting: Operation room. Patients and Methods: 75 ASA physical status I and II adult patients, aged 18-45 years undergoing elective surgical procedures, requiring general anesthesia and orotracheal intubation. Interventions: Patients were allocated to any of the three groups (25 each)-Group C (control)10 ml 0.9% saline i.v. Group E (esmolol) 0.5 mg/kg diluted with 0.9% saline to 10 ml i.v. Group L (labetalol) 0.25 mg/kg diluted with 0.9% saline to 10 ml i.v. In the control group 10 ml of 0.9% saline was given both at 2 and 5 min prior to intubation. In the esmolol group 0.5 mg/kg of esmolol (diluted with 0.9% saline to 10 ml) was given 2 min prior and 10 ml of 0.9% saline 5 min prior to intubation. In the labetalol group 10 ml of 0.9% saline was administered 2 min prior and 0.25 mg/kg of labetalol (diluted with 0.9% saline to 10 ml) 5 min prior to intubation. All the patients were subjected to the same standard anesthetic technique. Measurements: Heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded prior to induction, at time of intubation and 1, 3, 5, and 10 min after intubation. Mean arterial pressure (MAP) and rate pressure product (RPP) were calculated. Abnormal ECG changes were also recorded. Results: Compared to placebo and esmolol (0.5 mg/kg), labetalol (0.25 mg/kg) significantly attenuated the rise in heart rate, systolic blood pressure, and RPP during laryngoscopy and intubation. However, the difference was not statistically significant among the values for DBP and MAP. Conclusion: In lower doses, labetalol (0.25 mg/kg) is a better agent than esmolol (0.5 mg/kg) in attenuating the sympathomimetic response to laryngoscopy and intubation.

Keywords: Labetalol, esmolol, sympathomimetic, response, intubation


How to cite this article:
Singh SP, Quadir A, Malhotra P. Comparison of esmolol and labetalol, in low doses, for attenuation of sympathomimetic response to laryngoscopy and intubation. Saudi J Anaesth 2010;4:163-8

How to cite this URL:
Singh SP, Quadir A, Malhotra P. Comparison of esmolol and labetalol, in low doses, for attenuation of sympathomimetic response to laryngoscopy and intubation. Saudi J Anaesth [serial online] 2010 [cited 2019 Oct 14];4:163-8. Available from: http://www.saudija.org/text.asp?2010/4/3/163/71573


  Introduction Top


Despite the emergence of new airway devices in the recent years, rigid laryngoscopy and tracheal intubation still remain the gold standard in airway management. The hemodynamic changes stemming from airway instrumentation are due to sympathoadrenal discharge caused by epipharyngeal and parapharyngeal stimulations. There is increase in heart rate (HR), blood pressure, intraocular, and intracranial pressure. The arterial hypertension is due to increase in cardiac output rather than an increase in systemic vascular resistance, and is associated with the transient rise in central venous pressure. Arrhythmias also tend to occur.

The major conditions in which these responses may pose serious challenges are cardiovascular diseases like hypertension, coronary artery disease, aneurysmal vascular disease or those with decreased intracranial compliance like head injury with extra or intradural hematoma formation, intracranial tumors, etc. A sudden rise in blood pressure may cause left ventricular failure, myocardial ischemia, and cerebral hemorrhage. These complications are more likely in the presence of coronary or cerebral atheroma or hypertension. Also convulsions may be precipitated in pre-eclamptic patients.

Various attempts have been made to suppress this pressor response. The pharmacological methods are aimed at efferent, afferent, or both limbs of response e.g. volatile inhalational agents, [1] lignocaine, [2] opioids, [3] sodium nitroprusside, [4] nitroglycerine [5] calcium channel blockers, [6] and adrenergic blockers. [7]

Most workers have used esmolol [8],[9],[10],[11],[12] (cardioselective beta blocker) as a bolus and in infusion and found it to be effective. Other beta blockers like metoprolol [13],[14] and labetalol [15],[16],[17],[18] have been useful in not only attenuating the response of laryngoscopy and intubation but also in preventing perioperative cardiovascular events. However studies comparing esmolol with labetalol (non selective adrenergic blocker) as an attenuating agent for pressor response are lacking.


  Patients and Methods Top


Study design

This study was a prospective, randomized, placebo controlled, double-blinded trial comparing two adrenergic antagonists labetalol (nonselective) and esmolol (B1 selective) in decreasing the pressor response during rigid laryngoscopy and intubation. The protocol was approved by the Institutional Review Board and was in accordance with International Conference on Harmonisation; Good Clinical Practice (ICH-GCP) standards.

Duration of study

March 2006 - August 2007

Sample

Sample size was calculated by power analysis, using a two-sample t0 test, with a two-sided type I error of 5% (α=0.05) and power at 80.37 (α=0.19). Therefore, 75 patients, ASA physical status I and II, aged 18-45 years, undergoing elective surgical procedures, requiring general anesthesia and orotracheal intubation were included in the study. Informed consent was obtained from all the patients. Patients with cardiovascular, pulmonary, hepatic, and renal disease; those on B blockers; patients with difficult airway; laryngoscopy and intubation time more than 30 s, or requiring more than two attempts were excluded from the study.

Procedure

The patients were randomly (computer generated randomization schedule) allocated into one of the three groups, of 25 each. Blinding was done using the SNOSE (sequentially numbered opaque sealed envelope) technique. Patients were allocated to any of the three groups-

Group C (control) 10 ml 0.9% saline i.v.

Group E (esmolol) 0.5 mg/kg diluted with 0.9% saline to 10ml i.v.

Group L (labetalol) 0.25 mg/kg diluted with 0.9% saline to 10ml i.v.

In the control group 10 ml of 0.9% saline was given both at 2 and 5 min prior to intubation. In the esmolol group 0.5 mg/kg of esmolol (diluted with 0.9% saline to 10 ml) was given 2 min prior and 10 ml of 0.9% saline 5 min prior to intubation. In the labetalol group 10 ml of 0.9% saline was administered 2 min prior and 0.25 mg/kg of labetalol (diluted with 0.9% saline to 10 ml) 5 min prior to intubation.

Patients were kept nil orally for 8 h prior to surgery.

All patients were premedicated intravenously 10 min prior to induction with inj. ondansetron 0.1 mg/kg, inj. tramadol 2 mg/kg, and inj. midazolam 0.05 mg/kg.

The patients were pre-oxygenated with 100% 02 by a face mask for 3 min. Induction was done with inj. thiopentone 5 mg/kg and after 30 s relaxation achieved with inj rocuronium bromide 1 mg/kg. 90s later the patient was intubated using a Macintosh laryngoscope. All intubations were done by the same experienced laryngoscopist. Tracheal tubes of ID 7.0 mm and 8.0 mm were used for female and male patients, respectively. Anesthesia was maintained by N 2 O (60%) and O 2 (40%), intermittent boluses of vecuronium bromide intravenously and propofol infusion (5 mg/kg/hr). At the end of surgery, neuromuscular blockade was reversed with inj. neostigmine (40 μg/kg) and inj. atropine (20 μg/kg).

Measures

HR, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were recorded prior to induction, at time of intubation and 1, 3, 5, and 10 min after intubation. Mean arterial pressure (MAP) and rate pressure product (RPP) were calculated for the same time stations. Abnormal ECG changes were also recorded.

Statistics analysis

Statistical analysis was performed using the SPSS software version 13 (Chicago, IL, USA). Patient demographics were compared with analysis of variance (ANOVA). The study data were analyzed using statistical methods of mean, standard deviation, paired students "t" test (for values within the group at different time stations) and independent samples "t" test (for comparison of intergroup values).


  Results Top


The patients in the three groups were comparable with respect to age, weight, sex, and duration of surgery or anesthesia [Table 1].
Table 1: Demographic data

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The preinduction values of pulse rate (PR) were comparable between groups with no significant difference [Table 2].There was no statistically significant difference in PR throughout study time between the esmolol and control groups (P>0.05). At intubation and 1 min postintubation PR was significantly lower in the labetalol group compared to the control group (P<0.001and P=0.012 respectively). At 3 and 5 min postintubation, there was no significant difference in PR (P=0.17 and P=0.37 respectively) between labetalol and control groups. At 10 th minute PR was significantly lower in the labetalol group than the control group (P<0.001). The PR were significantly less in the labetalol group throughout the study time compared with the esmolol group (<0.001 at intubation and 1 st minute postintubation, P=0.02 at 3 rd minute, P=0.01 at 5 th and P<0.001 at 10 th minute postintubation).
Table 2: Pulse rates

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The preinduction values of SBP were comparable between groups with no significant difference [Table 3]. SBP increased in both esmolol and control groups at all times. However, no significant difference was present between the groups (P>0.05). Compared with the control group values [Table 3] SBP was significantly lower at all time stations in the labetalol group (P<0.001 at intubation, 1 st and 3 rd minute postintubation; P=0.004 at 5 th minute and P=0.02 at 10 th minute postintubation). SBPs were significantly less in patients receiving labetalol compared to those who received esmolol (P<0.01 at intubation and 1, 3 and 10 min postintubation and P=0.014 at 5 min postintubation).
Table 3: Systolic blood pressures

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The preinduction values of DBP were comparable between groups with no significant difference [Table 4]. [Table 4] shows that DBP at 1 minute postintubation in the esmolol group was significantly less than that in the control group (P=0.028). At all other times it was comparable between the groups (P>0.05). DBP in the labetalol group was comparable with the control group with no significant difference. Diastolic pressures were not significantly different between labetalol and esmolol groups (P>0.05).
Table 4: Diastolic blood pressures

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The preinduction values of MAP were comparable between groups with no significant difference [Table 5]. MAP was significantly less at the time of intubation in the esmolol group (P<0.05) compared with the control group. All other postintubation values were comparable between the two groups and not statistically significant (P>0.1). Compared with controls [Table 5], it was significantly less in the labetalol group at all times except at 10 th minute postintubation (P=0.012 at intubation, P<0.01 at 1 st and 3 rd minute postintubation, P=0.04 at 5 th minute and P=0.22 at 10 th minute postintubation). There was no statistically significant difference between values of labetalol and esmolol groups (P>0.15), except at 1 min postintubation when it was significantly less in the labetalol group (P=0.042).
Table 5: Mean arterial pressures

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The preinduction values of RPP were comparable between groups with no significant difference [Table 6]. RPP was significantly less at the time of intubation in the esmolol group (P<0.05) as compared to the control group. All other postintubation values were comparable between the groups and not statistically significant (P>0.1). RPP values were lower in the labetalol group compared to the control group [Table 6]. The difference was statistically significant at all times (P<0.001 at intubation, 1 st , 3 rd and 10 th minute postintubation and P=0.03 at 5 th minute postintubation). RPP was significantly lower in the labetalol group at all times (P<0.001 at intubation and 1 and 10 minutes postintubation and P<0.01 at 3 rd and 5 th minute postintubation). The RPP in the labetalol group never crossed the critical 15000 mark.
Table 6: Rate pressure products

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Three episodes of atrial ectopics were recorded just after intubation in control (two episodes: at time of intubation and 3 min postintubation) and esmolol groups (1 min postintubation). Twenty eight (7 of 25) percent patients in the labetalol group developed bradycardia (pulse rate<50 beats per minute) after study period of 10 min.


  Discussion Top


Most of the clinicians use adjuncts to attenuate the sympathetic response associated with laryngoscopy and intubation in high risk patients. Beta blockers have been compared with fentanyl, [3] nitroprusside, [4] nitroglycerine, [5] calcium channel blockers, [6] etc; however, studies comparing esmolol [8],[9],[10],[11],[12] (cardioselective beta blocker) and labetalol [15],[16],[17],[18] (nonselective adrenergic blocker) are lacking.

Esmolol hydrochloride is an ultra-short acting, beta-one selective adrenergic receptor blocker with a distribution half-life of 2 min and an elimination half-life of 9 min. Esmolol appears quite suitable for use during a short-lived stress such as tracheal intubation or ECT. Labetalol is an adrenergic receptor blocking agent with mild alpha1- and predominant beta-adrenergic receptor blocking actions (alpha:beta blockade ratio of 1:7 for iv and 1:3 for PO administration). The onset of action of i.v. labetalol is 5 min.

We studied the hemodynamic response to laryngoscopy and intubation for a period of 10 min as this is the average period for which hemodynamic changes are believed to last. [19]

There was no significant effect of esmolol on PR when compared to the control group. Labetalol had a significantly (P<0.05) better effect than esmolol in controlling PR at all points during the study. It seems that when instrumentation stimulus is present labetalol maintains the PRs within normal ranges. When the effect of stimulus weans off, as occurs at 10 min postintubation, the drug`s effect takes over and pulse rates go below baseline values.

In preventing the increases in SBP esmolol was completely ineffective as there was no significant difference between values of esmolol and control groups during the study period (P>0.05). Labetalol prevented the increase in SBP significantly throughout the study period as compared to control and esmolol groups (P<0.05). Ramanathan et al.[18] used 20 mg labetalol to prevent rise in SBP successfully. Inada et al.[17] found 10 mg (0.14 mg/kg) labetalol ineffective in attenuating the rise in systolic pressure. This difference might be because of the lower dose they used and the timing of giving of labetalol (2 min prior to intubation) because of which the peak effect of drug was lost at intubation. Maharaj et al.[20] failed to blunt the blood pressure response with 0.25 and 0.5 mg/kg labetalol. However, they did not mention the timing of giving the drug. Esmolol even in doses exceeding >1mg/kg have been found to be ineffective in controlling systolic pressure rise.

When compared to controls the rise in DBP was not attenuated (P>0.05) in any of the study groups [Table 4]. There was a significant difference between esmolol and control values at 1 minute postintubation (P<0.05). This was an isolated finding because no significant difference was observed at subsequent points of study. In intergroup comparison of esmolol and labetalol, none of them was found to be better (P>0.05).

Comparing the esmolol group with controls [Table 5] revealed that the esmolol group had a significantly less MAP at intubation (P=0.044). This observation is the same as made by Sharma et al.[8] and Bakiye et al.[21] in their studies, although esmolol was not at all effective in controlling MAP rise after laryngoscopy and intubation (P>0.05). When the labetalol group was compared with the control group the MAP was significantly less at all points (P<0.05) except at 10 min postintubation when the values were comparable. Between esmolol and labetalol there was no significant difference in values except at 1 min postintubation (labetalol having lower MAPs). This observation was again an isolated finding and no significant difference (P>0.05) was found at any other point during the study period. MAP increase was attenuated by labetalol but not esmolol.

In esmolol-treated patients RPP was not significantly different from the control group. Compared to control and esmolol groups, the labetalol group had significantly lower values of RPP [Table 6]. Labetalol could not prevent the increase in RPP completely (significantly elevated at intubation and at 1 min postintubation). However, the magnitude of increase was less and never crossed the critical limit of 15000 mmHg/min. The values returned to baseline at 3 min postintubation as compared to other groups where they achieved baseline values after 10 min. Therefore, labetalol (0.25 mg/kg) decreases the magnitude and duration of hemodynamic response to laryngoscopy as evident from changes of RPP. Leslie et al.[22] used labetalol in doses of 0.25, 0.5, 0.75 and 1.0 mg/kg and found all doses effective in controlling the rise in RPP at laryngoscopy.

The only side effect observed was that of labetalol in form of bradycardia, intraoperatively. Seven patients (28 %) developed bradycardia (pulse rate <50 beats per minute) after the study period of 10 min and had to be given atropine in 0.2 mg increments (max. 0.01 mg/kg). All the patients responded to atropine treatment. There were no recurrent episodes of bradycardia. No other side effects were observed. We recorded three episodes of atrial ectopics just after intubation. The atrial ectopics recorded in our study were attributed to tracheal intubation and not thiopentone induction. [23],[24] All three ectopics occurred at the time of intubation or just after the intubation and there were no abnormal ECG changes between the duration of induction and intubation.


  Conclusion Top


In lower doses, labetalol (0.25 mg/kg) is a better agent than esmolol (0.5 mg/kg) in attenuating the sympathomimetic response to laryngoscopy and intubation whereas low dose esmolol (0.5 mg/kg) is ineffective for the same purpose. Bradycardia is a potential side effect of labetalol.

 
  References Top

1.Bedford RE, Feinstein B. Hospital admission blood pressure predictor for hypertension following endotracheal intubation. Anesth Analg 1980;59:367-70.  Back to cited text no. 1      
2.Stoelting RK. Blood pressure and heart rate changes during short duration laryngoscopy for tracheal intubation: influence of viscous or intravenous lidocaine. Anesth Analg 1978;57:197-9.  Back to cited text no. 2      
3.Martin DE, Rosenberg H, Aukburg SJ, Bartkowski RR, Edwards MW Jr, Greenhow DE, et al. Low dose fentanyl blunts circulatory responses to tracheal intubation. Anesth Analg 1982;61:680-4.  Back to cited text no. 3      
4.Stoelting RK. Attenuation of blood pressure response to laryngoscopy and tracheal intubation with sodium nitroprusside. Anesth Analg 1979;58:116-9.  Back to cited text no. 4      
5.Kamra S, Wig J, Sapru RP. Topical nitroglycerine. A safeguard against pressor response to tracheal intubation. Anaesthesia 1986;41:1087-91.  Back to cited text no. 5      
6.Mikawa K, Nishina K, Maekawa M, Obara H. Comparison of nicardipine, diltiazem and verapamil for controlling the cardiovascular responses to tracheal intubation. Br J Anaesth 1996;76:221-6.  Back to cited text no. 6      
7.Nami K, Takahi K, Tanaka K, Shuzo O. A comparison of landiolol and esmolol for attenuation of cardiovascular response and plasma rennin activity against tracheal intubation with laryngoscopy. Anesthesiology 2005;103:433.  Back to cited text no. 7      
8.Sharma S, Mitra S, Grover VK, Kalra R. Esmolol blunts the haemodynamic responses to tracheal intubation in treated hypertensive patients. Can J Anaesth 1996;43:778-82.  Back to cited text no. 8      
9.Ebert TJ, Bernstein JS, Stowe DF, Roerig D, Kampine JP. Attenuation of hemodynamic responses to rapid sequence induction and intubation in healthy patients with a single bolus of esmolol. J Clin Anesth 1990;2:243-52.  Back to cited text no. 9      
10.Rathore A, Gupta HK, Tanwar GL. Attenuation of the pressure response to laryngoscopy and endotracheal intubation with different doses of esmolol. Indian J. Anaesth 2002;46:449-52.  Back to cited text no. 10      
11.Oda Y, Nishikawa K, Hase I, Asada A. The short-acting ί1-adrenoceptor antagonists esmolol and landiolol suppress the bispectral index response to tracheal intubation during sevoflurane anesthesia. Anesth Analg 2005;100:733-7.  Back to cited text no. 11      
12.Oxorn D, Knox JW and Hill J. Bolus doses of esmolol for the prevention of perioperative hypertension and tachycardia. Can J Anaesth 1990;37:206-09.  Back to cited text no. 12      
13.Zargar JA, Naqash IA , Gurcoo SA, Mehraj-ud-din. Effect of Metoprolol and esmolol on rate pressure product and ECG changes during laryngoscopy and tracheal intubation in controlled hypertensive patients. Indian J Anesth 2002;46:365-8.  Back to cited text no. 13      
14.Magnusson J, Werner O, Carlsson C Norden, N, Pettersson, KI. Metoprolol, fentanyl and stress response to micro laryngoscopy. Effect on arterial pressure, heart rate and plasma concentration of catecholamines, ACTH and Cortisol. Br J Anaesth 1983;55:405-14.  Back to cited text no. 14      
15.Kim HY, Chung CW, Lee HY, Yim CH. The Effect of labetalol on the hemodynamic response to endotracheal intubation. Korean J Anesthesiol 1994;27:1611-9.  Back to cited text no. 15      
16.Chung KS, Sinatra RS, Chung JH. The effect of an intermediate dose of labetalol on heart rate and blood pressure response to laryngoscopy and intubation. J Clin Anesth 1992;4:11-5.  Back to cited text no. 16      
17.Inada E, Cullen DJ, Nemeskal R, Teplick R. Effect of labetalol on the hemodynamic response to intubation: a controlled, randomized double-blind study. J Clin Anesth 1989;1:207-13.  Back to cited text no. 17      
18.Ramanathan J, Sibai BM, Madie WC, Chauhan D, Ruiz AG. The use of labetalol for attenuation of hypertensive response to endotracheal intubation in preeclampsia. AM J Obstet Gynecol 1988;159:650-4.  Back to cited text no. 18      
19.Forbes AM, Dally FC. Acute hypertension during induction of anaesthesia and endotracheal intubation in normotensive man. Br J Anaesth 1970;42:618-24.   Back to cited text no. 19      
20.Maharaj RJ, Thompson M, Brock JG, Williamson R, Downing JW. Treatment of hypertension following endotracheal intubation. A study comparing the efficacy of labetalol, practolol and placebo. S Afr Med J 1983;63:691-4.  Back to cited text no. 20      
21.Bakiye U, Ogurlu M, Gezer E. Effects of esmolol, lidocaine and fentanyl on haemodynamic responses to endotracheal intubation: A comparative study. Clinical Drug Investigation 2007;27:269-77.  Back to cited text no. 21      
22.Leslie JB, Kalayjian RW, Mc Loughlin TM, Plachetka JR. Attenuation of hemodynamic response to endotracheal intubation with pre induction intravenous labetalol. J Clin Anesth 1989;1:194-200.  Back to cited text no. 22      
23.Gauthier J, Bosomworth P, Page D, Moore F, Hamelberg W. Effect of endotracheal intubation on ECG patterns during halothane anesthesia. Anesth Analg 1962;41:466-70.  Back to cited text no. 23      
24.Rollason WN, Hough JM. Thiopentone induction and electrocardiogram. Br J Anaesth 1958;30:50-62.  Back to cited text no. 24      



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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