A comparative study of esmolol versus dexmedetomidine in attenuation of cardiovascular response following laryngoscopy

R Gowthaman¹, M Shanmugavalli^2*

Abstract               Objectives: To compare the safety and efficacy of esmolol versus dexmedetomidine in attenuation of cardiovascular response to laryngoscopy. Study design: Randomized controlled clinical trial. Place and duration of study: Rajah Muthiah Medical College, Chidambaram, 2017-2018.Methodology:After acceptance from the department of ethical committee and written informed consent from all patients, a single blinded RCT was conducted on 50 patients (n=50) aged 20–45 years (both sex) of ASA I-II who are posted for elective surgery. They were chosen randomly and allocated into 2 different groups, group A and group B with 25 members in each group. All patients were premedicated with inj.Glycopyrrolate 0.2 mg IM 45 min before induction. Group A received inj. Esmolol 1.5 mg / kgand Group B received Dexmedetomidine 1µg / kg iv. After induction with inj.Thiopentone 5mg/kg and inj. Succinyl choline 2mg/kg, laryngoscopy and ET intubation was done. N2O: O2 mixture- 65:35 and 2% sevoflurane were used as maintenance anaesthesia during intraoperative period.Haemodynamic variables like HR, SBP, DBP and MAP were recorded for both groups before induction, immediately post Intubation, 5 min, 10 min, 15 min, 20 min and 30 min post intubation. Data was analysed and compared. Results: Dexmedetomidine 1µg / kg given intravenously ten minutes preceding induction, obtunded the pressor response post laryngoscopy andETintubation to a statistically significant level compared to Esmolol. Conclusion: Debilitation of pressor response is noted with both Dexmedetomidine and Esmolol. Among the twodrugs Dexmedetomidine 1 µg/kgi.v bolus provides consistent and more effective debilitation than Esmolol 1.5 mg/kg i.v bolus.

Key Word:Dexmedetomidine, Esmolol, laryngoscopy, intubation.

INTRODUCTION

Inspite of advances in airway management, Rigid laryngoscopy and ET intubation are still the gold standard in General anaesthesia¹.Reid and Brace in 1940² described the haemodynamic pressor response due to laryngeal and tracheal stimulation during laryngoscopy and ET intubation. These haemodynamic responses, increase the release of catecholamine resulting in increase in heart rate, increase in blood pressure and occasional disturbance in cardiac rhythm^3,4,5,6.The consequent rise in rate/pressure product may increase the myocardial oxygen demand which overrides the supply resulting in myocardial ischaemia⁷.These haemodynamic changes usually last for only 5- 10 minutes, which peak at 1 minute⁸. The rise in heart rate, BP is usually short lived and not predictable. These haemodynamic alterations are well coped by healthy individual, but can be detrimental to cardiac patients. Several methods have been used to debilitate the pressor response during laryngoscopy and ET intubation, but each has its own advantages and disadvantages. Many drugs have been tried to blunt this response which includes Lidocaine, Alpha blockers, Beta blockers, Ca²⁺channel blockers, Sodium nitroprusside, Nitroglycerine and Opioids^1,.5,9,10.Dexmedetomidineis highly selective centrally acting, potent α₂ agonist and is more selective than clonidine( ratios of α₂ :α₁ activity , 1620:1 for dexmedetomidine, 220:1 for clonidine). Also, Dexmedetomidine is faster acting than clonidine. Among Beta blockers, Esmolol, a cardioselective drug which has extremely shorter duration of action. However there is lack of clinical trials showing comparative study between dexmedetomidine and esmolol in debilitation of cardiovascular response following laryngoscopy. On this background, we compared the safety and efficacy of dexmedetomidine versus esmolol in debilitation of cardiovascular response to laryngoscopy and intubation.

MATERIALS AND METHODS

Patients were chosen randomly and allocated into two different groups with 25 members in each group. The study was carried out as a single blinded RCT.

Group A:(Esmolol 1.5 mg/ kg)–25 patients received Esmolol 1.5 mg / kg IV,two minutes preceding induction.

Group B:(Dexmedetomidine 1µg / kg)–25 patients received Dexmedetomidine 1µg / kg IV, ten minutes preceding induction. A thorough pre-anaesthetic evaluation done.

All patients received pre-operative night sedation tab. Diazepam 10 mg P.O and tab. Ranitidine 150 mg P.O at bed time on the previous night .Inj.glycopyrolate 0.2 mg IM was given to all patients included in this study as premedicant 45 mins before surgery .After shifting the patient to operating table,patients were connected to baseline monitors. Intravenous access established with 18 G IV cannula and intravenous fluids started. Pulse rate,BP, ECG, SPO₂ recorded. All patients were pre oxygenated with 100% oxygen for three mins via face mask.Inj fentanyl 1µg/kg given 3 minutes preceding induction. All patients received study drug in a randomized manner either inj. Esmolol1.5 mg/kg body weight (group A) two minutes preceding induction or inj. Dexmedetomidine 1µg/kg ( Group B) 10 minutes preceding induction. The study drug was diluted with 10 ml of normal saline. Patient was induced with 2.5% Thiopentone sodium till the termination of eyelash reflex. After termination of eyelash reflex inj. Suxamethonium 2mg/kg was administered intravenously. Endotracheal intubation was accomplished with Macintosh laryngoscope orally after complete paralysis. ET tube was secured in patients within 15 seconds, requiring not more than 2 attempts. Appropriate size endotracheal tube was secured, 7-7.5 mm endotracheal tube for adult females and 8-8.5 endotracheal tube for adult males and confirmed by five point auscultation. Cuff inflated, position confirmed and connected to Bain’s circuit. N₂0: 0₂mixture - 65:35 and trace of volatile agent were used as maintenance anaesthesia during intraoperative period.Inj.vecuronium bromide 0.08 mg/ kg loading dose and one fourth of initial dose were used as maintenance. BP, heart rate, SPO₂ and ECG tracing were recorded and this was taken as post intubation value. Thereafter readings were taken every 5 minutes until 30 minutes post intubation.

OBSERVATION

In this study, mean age (in years) in Group A- 29 and in Group B – 31.64.

The mean weight (in kgs) in Group A –56.36 and in Group B–53.28.

In Group A, the mean HR was 93.88 ±8.70(pre-induction) and post intubation the mean HR found to be 93.71±7.41. In Group B, the mean HR was 89.84±6.35 (pre-induction) and post intubation the mean HR decreased to 73.13±5.27.

In Group A, the mean SBP was 124.40±8.70 (pre- induction) and post intubation the mean SBP found to be 124.79±15.72. In group B, the mean SBP was 128.80±6.35 (pre-induction) and post intubation the mean SBP decreased to 104.63±9.29.

In Group A, the mean DBP was 83.68±9.86 (pre-induction) and post intubation the mean DBP found to be 86.73±9.93. In Group B, the mean DBP was 84.48±9.39 (pre-induction) and post intubation the mean DBP decreased to 73.55±6.20.

In Group A, the mean MAP was 97.25±9.84 (pre-induction) and after intubation the mean MAP found to be 99.41±11.31. In Group B, the mean MAP was 99.25±8.64 (pre-induction) and post intubation the mean MAP decreased to 71.62±6.12.

The Thiopentone dosage requirement decreased in approximately 60% (n=15) of the individual in Group B as compared to Group A which is statistically significant (P<0.0001).

Postoperatively among Group B patients 24% (n=6) had sedation score of 3, 28% (n=7) has sedation score of 4 , 48% (n=12) had sedation score of 5.

RESULTS

Table 1:Age distribution between two groups

The mean age of the patients in Group A is 29±8.24 The mean age of the patients in Group B is31.64±6.85

Table 2: Sex distribution between two groups

In group A 28%(7) were males and 72% (18) were females. In group B 40% (10) were males and 60% (15) were females.

Table 3:Weight distribution between two groups

The mean weight of patients in Group A is 56.36±8.87. The mean weight of patients in Group B is 53.28±11.09

Table 4: Comparison of Thiopentone dosages between two groups

The above table shows thiopentone dosage requirement in both the study groups. The dosage requirement was decreased in approximately 60% (n=15) of the individual in Group B as compared to Group A which is statistically significant (p<0.0001)

Table 5: Comparison of Post OP Sedationdosages between two groups

Postoperatively among Group B patients 24% (n=6) has sedation score of 3, 28% (n=7) has sedation score of 4, 48% (n=12) has sedation score of 5. Group A Patients did not have any sedative effects.

Table 6: Comparison of Pre and Post Intubation Mean Heart rate between two groups

The mean heart rate decreased to about 0.18% in 44% of the individual in group A post intubation which is not statistically significant. The mean heart rate decreased to about 18.60% in all the individuals of Group B.

Table 7:Comparison of Pre and Post Intubation Mean SBP between two groups

The mean systolic BP is increased to about 0.38% in 48% of the individual in group A post intubation which is not statistically significant. The mean systolic BP is decreased to about 18.77% in all the individuals of Group B.

Table 8:Comparison of Pre and Post Intubation Mean DBP between two groups

The mean diastolic BP is increased to about 3.65% in 44% of the individual in group A which is not statistically significant. The mean diastolic BP is decreased to about 12.93% in all the individuals of Group B.

Table 9:Comparison of Pre and Post Intubation Mean MAP between two groups

The MAP is increased to about 2.21% in 40% of the individual in group A which is not statistically significant. The MAP is decreased to about 27.84% in all the individuals of group B.

DISCUSSION

Haemodynamic response to laryngoscopy and ET intubation was first described by Reid and Brace in 1940². Following laryngoscopy and ET intubation increase in heart rate, BP occurs as a result of release of catecholamines. These haemodynamic responses are well coped by healthy individual but, become detrimental in group of patients having ischaemic heart disease, hypertension, intracranial aneurysm, cerebrovascular accidents etc.It is for these reasons, various studies had been conducted to find effective methods to attenuate this pressor response. In our study, we had done comparative analysis between Dexmedetomidine and Esmololas which drug obtunded the pressor response better. This was demonstrated in 50 patients of ASA I-II and divided into two different groups with 25 members in each group. Group A was given Esmolol 1.5 mg/ kg and Group B was given Dexmedetomidine 1µg/kg bodyweight to debilitate the pressor response to laryngoscopy. Hemodynamic parameters like HR, systolic blood pressure, diastolic blood pressure were measured at different time intervals until 30 minutes post intubation. Esmolol (1.5mg/kg), an ultrashort acting β- blocker is given in Group A patients and Dexmedetomidine (1µg/kg), highly selective α₂ agonist, sedative, anxiolytic is given in Group B patients. Esmolol hydrochloride which is an ultrashort acting cardioselective β blocker has distribution half life of 2 minutes and elimination half life of 9 minutes and when it is given two minutes preceding induction it decreases the pressor response better. Miller et al.(1989)¹¹ concluded that esmolol 100mg given as bolus  obtunded the pressor response better in a Canadian multicentre trial. However in our study it was found that Esmolol (1.5mg/kg) significantly reduced the heart rate response but BP increase was not significant .Oxorn et al.(1990)¹² found out esmolol when given 100mg and 200 mg as bolus doses significantly decreased the heart rate response. Kindler et al   .(1996)¹³ concluded that heart rate response to intubation reduced when esmolol given preceding induction but at the same time it failed to obtund the rise in SBP. Hale Yarkan Uysal et al.(2012)¹⁴ concluded that in hypertensive patients esmolol was very effective in obtunding the heart rate response, but failed to debilitate the blood pressure response to ET intubation. Vucovic M et al   .(1992)¹⁵ concluded that esmolol when given two minutes preceding induction did not obtund the haemodynamic response which is same as our duration of drug administration. Vucovic M et al.(1992)¹⁵ also concluded that when esmolol(500mcg/kg/min) given two minutes preceding induction with maintenance dose 100mcg/kg/min till intubation, obtunded the haemodynamic response significantly which did not happen in our study. Kovac et al   .(1992)¹⁶studied that in any patients in whom rise in heart rate is detrimental, esmolol when given preceding induction obtunded the HR response significantly. Dexmedetomidine highly selective α₂agonist, sedative, analgesic, anxiolytic blunts pressor response to laryngoscopy which is being extensively studied. These responses are mediated through activation of α₂ receptors which is involved in regulating cardiovascular and autonomic system. α₂receptors which are located post synaptically, when activated result in sedation, decreased neuronal activity and increased vagal activity^{17,18,19,20,21,22,23}. Our study focuses on Dexmedetomidine(1µg/kg)when given 10 minutes preceding induction obtunds the haemodynamic response significantly.  Scheinin’s et al   .²⁴concluded that dexmedetomidine 0.6µg/kg obtunded the haemodynamic response well and reduced the thiopentone dosage requirements. Ozkose et al.²⁵ in his study found that dexmedetomidine 1µg/kg obtunded the haemodynamic response significantly i.e. decreased the heart rateupto 15% and decreased mean arterial pressure response up to 20% 1^st and 3rd minute following intubation. Khan et al.²⁶ found that HR, SBP ,DBP were notably decreased bydexmedetomidine. Yildiz et al.²⁷ demonstrated that dexmedetomidine(1µg/kg) obtunds the pressor response post laryngoscopy significantly which is the same case in our study also. Talke P et al. noted that dexmedetomidine infusions led to the suppression of HR and plasma catecholamine in the immediate postoperative period in vascular surgery patients²⁸. Jaakola et al.²⁹ demonstrated that dexmedetomidine(0.6µg/kg) obtunds the pressor response post laryngoscopy significantly .Sukhminderjit Singh Bajwa et al³⁰ ,Ozkose et al²⁵, Aho et al³¹, Yildiz et al²⁷, Ferdi Menda et al³² concluded from their studies thatdexmedetomidine(1µg/kg) attenuates the hemodynamic response significantly as of our study.In our study, comparative analysis showed that both the drugs attenuated the pressor response significantly. Esmolol(1.5mg/kg), as demonstrated by Kindler et al   .¹³ and Yarkan Uysal et al.¹⁴ obtunds the HR response but failed to decrease BP and its increase is also not significant. Dexmedetomidine at a dosage of 1µg/kg, as already demonstrated by Sukhmindherjit Singh Bajwa et al³⁰, Ozkose et al²⁵, Aho et al³¹, Yildiz et al²⁷ showed statistically significant reduction in haemodynamic response when related to esmolol group. In our study, there was no remarkable ECG changes or SPO2 level in either of the groups at all time period. There was nohypoxia, apnea or airway obstruction with bolus dose of dexmedetomidine in our study³³.

CONCLUSION

Debilitation of pressor response noticed in bothDexmedetomidineandEsmolol. Among the twodrugs,Dexmedetomidine 1 µg/kgIV bolus provides consistent and more effective decrease than Esmolol 1.5 mg/kg IV bolus.

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