European Journal of Cardiovascular Medicine

Laryngoscopy and endotracheal intubation is accompanied by intense sympathomimetic stimulation resulting in increase in Heart Rate (HR) and arterial Blood Pressure (BP). This effect is caused by the release of catecholamines¹.

The exact mechanism of this hemodynamic response is not clear till date. The magnitude of this hemodynamic response is multifactorial such as the anesthetic drug used, prior medication, depth of anesthesia, duration of laryngoscopy and intubation etc. This sympatho-adrenergic response is transient and less significant in healthy individuals. But in patients with reduced myocardial reserve/hypertension / cerebro-vascular insufficiency/raised intracranial or intraocular pressure this response is very hazardous and may predispose to pulmonary edema / myocardial infarction/ cerebro-vascular accident /dysrhythmias".

To minimize these hemodynamic adverse effects, multiple non-pharmacological methods and pharmacological agents have been tried before intubation which acts at different levels of reflex arc²

The non-pharmacological method tried was minimizing mechanical stimuli of laryngoscopy by blind nasal intubation and reducing time of laryngoscopy to < 15 seconds³

Various authors have attempted to block the peripheral sensory receptors and afferent input by topical application of Local Anesthetics (LA) and infiltration of the glossopharyngeal nerve and superior laryngeal nerve⁴.

The central sensory receptors were blocked by using Intravenous (IV) Fentanyl⁵, Morphine etc. The efferent pathway have been blocked by using IV Lignocaine", B-blockers, Calcium Channel Blockers (CCB), vasodilators [Sodium Nitroprusside (SNP)15, Nitroglycerine (NTG), Magnesium Sulphate (MgSo4)⁶] etc.

None of the above-mentioned methods were effective in reducing the sympathetic response of intubation. Later alpha 2 agonist, a sympatholytic agent was tried. Apart from minimizing the hemodynamic adverse response, these drugs also have additional sedative, anxiolytic and analgesic effects" Clinically available 2-adrenergic agonists at present are Clonidine and Dexmedetomidine. Both Clonidine and Dexmedetomidine acts on a- and a- receptors and Dexmedetomidine is highly selective a-2 adrenergic agonist. Dexmedetomidine is 1620 times highly selective to a-2 receptor when compared to Clonidine which binds only 220 times selectively to a-2 receptor

Clonidine is an imidazoline derivative that suppress the pressor response to laryngoscopy and endotracheal intubation at a dosage of 3-5 mcg/kg orally given 90 minutes prior to the procedure or 1-3 mcg/kg IV infused over 10 minutes and administered 15 minutes prior to the procedure".

Dexmedetomidine is a lipophilic a methylol derivative and has shorter duration of action when compared to Clonidine. Dexmedetomidine is currently used in the Intensive care unit for sedation and as analgesia in mechanically ventilated patients which produces rapid recovery after discontinuation". Dexmedetomidine administered at a dose of 1 mcg/kg IV over 10 minutes is administered 15 minutes prior to the procedure, which effectively attenuates the hemodynamic response during the peri-operative period ^7,8. It has been found that the Minimum Alveolar Concentration (MAC) of volatile anesthetic agents decreases significantly upto 90% and so there is reduction in requirement of the induction drugs ^8,9.

In our study, we have compared the efficacy of Dexmedetomidine in reducing the hemodynamic stress response in two different doses (0.6 mcg/Kg and 1 mcg/Kg body weight) which was given prior to laryngoscopy and endotracheal intubation.

This study was conducted in Khaja Bandanawaz Teaching and General Hospital, Kalaburgi, Karnataka, India during the period of 10/09/2024 to 09/03/2025. This study was done after getting ethical committee clearance and informed written consent from all patients participated in this study.

Based on previous studies, the sample size for our study was determined as below,

• alpha = 0.05 Z alpha = 1.96 beta = 0.2 Z beta = 0.84 SD = 10.2
• N= 2 (Za + Z beta)² x 10. 2 ² /d² d = 10
• N = 80
• 80 patients of age group between 18-60 years belonging to ASA I and II posted for elective surgeries participated in this study.

INCLUSION CRITERIA:

• ASA 1 & 2 patients
• Adult patients aged between 18 & 60 years of both gender
• Elective surgeries under general anesthesia
• Mallampati class I & II

EXCLUSION CRITERIA:

• Patients with hypertension
• Patients on ẞ blockers
• Patients with bradycardia
• Patients with cardiac disease, coronary artery disease, cerebro vascular disease
• Patients with difficult airway
• BMI> 30 Kg/m²
• Pregnant patients & nursing mothers
• Patients of ASA grade 3 and above
• Patients with known hypersensitivity to study drug
• Emergency surgeries

Routine pre-operative assessment of all patients was done on the previous day of surgery. All the patients were premedicated with Tab. Alprazolam 0.5 mg on the night before surgery and Tab. Ranitidine 150 mg on the night before surgery & on the morning of surgery. Starvation guidelines included nil per oral intake (solids) from 10pm onwards on the previous day of surgery. After shifting the patient to the preoperative room on the day of surgery, they were randomly allocated to one of the two groups by random table number generated by computer. After shifting inside the operating room, baseline vital parameters like pulse rate, blood pressure and SpO2 were recorded with electronic monitor. Intravenous cannulation was done with 18-gauge cannula.

Group A patients: Received 0.6 mcg/kg Dexmedetomidine diluted in 100 ml normal saline 10 minutes prior to induction over 10 minutes.

Group B patients: Received 1 mcg/kg Dexmedetomidine diluted in 100 ml normal saline 10 minutes prior to induction over 10 minutes.

The study drug was prepared by the consultant in that operation theatre, according to the group allocation. Vital parameters like pulse rate, blood pressure, oxygen saturation were monitored and recorded every 5 minutes during and prior to induction. All the patients received normal saline 5ml/kg body weight post study drug infusion.Patients were preoxygenated with 100% oxygen for 3 minutes. inj. Glycopyrrolate 0.2 mg i.v and inj. Fentanyl 2 mcg/kg i.v were given and induced with inj. Propofol till the abolition of the eyelash reflex. After checking the adequacy of the mask ventilation, inj. Succinylcholine 1.5 mg/kg was given for intubation. Laryngoscopy and intubation was done with Macintosh blade laryngoscope after one minute and appropriate endotracheal tube was inserted. The time duration for laryngoscopy and intubation was recorded from the time of introduction of laryngoscopy till the placement of endotracheal tube beyond the vocal cords. The endotracheal tube was fixed after confirming the bilateral air entry by auscultation and EtCO2 monitor. Heart rate, systolic BP, diastolic BP, mean arterial BP and SpO2 was recorded after induction, at the time of intubation (0 minute), 1 min, 3rd min, 5th min and 10th min after intubation.

After intubation, anesthesia was maintained with Oxygen and Nitrous oxide at 1:2 ratio, Isoflurane 1% and inj. Vecuronium bromide was given. No surgical stimulus was given for the next 10 minutes.

STATISTICAL ANALYSIS:

All data were entered in Excel 2024 and statistical analysis was performed using the statistical software (SPSS) 30.0. Data were expressed as percentages and mean values (with standard deviations). Differences between groups were analyzed with the Independent Sample t-test for continuous variables and Pearson's Chi-square test for categorical variables. Paired sample t-test was used to compare the difference between pre and post values. Results were defined as statistically significant when the P value was less than 0.05.

Table 1: Age distribution between two groups

Age distribution of the patients in both the group in table 1 showed 32.65 ± 8.891 and 34.70 ± 10.16 in year is the mean age of group A and B respectively. It showed that was no significant statistical difference between group A and group B in age distribution to p value of 0.563.

Table 2: Sex distribution between two groups

There was no significants statistical difference in sex distribution between the two group according to statistics p value of 0.189

Table 3: Weight distribution between two groups

There was no significant statistical difference in weight distribution between two groups according to statistical p value of 0.369. the mean body weight for group A is 60.18 ± 8.56 and group B is 63.48 ± 10.88.

Table 4: Cormack Lehane grading in two groups

There was no significant statistical difference in Cormack Lehane grading between the two groups by statistical p value 0446

Table 5: side effects in two groups

There was no significant statistical difference between the two groups with regard to said effects p value corresponded to 0.602

Table 6: Intragroup comparison for heart rate between Group A & Group B

The baseline heart rate was comparable in both the groups as p value of 0.476. However 5^th , 10^th, 15^th, 20^th min, just before and post induction there was no statistical significance as the p value was > 0.05. there was a significant significance between the two groups in mean heart rate at the time of intubation, 1^st , 3^rd , 5^th , 10^th min after intubation as statistical p value of less than 0.05

Table 7. Intergroup comparison for SBP between Group A & Group B

The baseline mean SBP was comparable in both the groups as p value of 0.686.

There was a significant difference in mean SBP at 5^th, 10^th min after study drug administration and at 1^st min after intubation as statistical p value of less than 0.05

The baseline DBP was comparable in both the groups as p value of 0.344. There was a significant difference in mean DBP at the time of intubation, 1^st & 3^rd min after intubation as statistical p value less than 0.05.

In our study, we have compared the efficacy of Dexmedetomidine in reducing the hemodynamic stress response in two different doses (0.6 mcg/Kg and 1 mcg/Kg body weight) which was given just prior to laryngoscopy and endotracheal intubation.

The time duration of administering the drug in this study was similar to drug administration in Scheinin et al¹⁰ study and the drug was diluted in 100 ml of normal saline and infused slowly over 10 minutes. Rapid administration of the drug cause transient hypertension by stimulation of a₂ receptors in the periphery.

In group A (0.6 mcg/kg) after administring the study drug, there was a fall in heart rate from the baseline till induction and was statistically highly significant. After intubation, the heart rate increased but not more than the baseline value, however it attenuated the hemodynamic stress response of laryngoscopy and intubation.

This finding was inconsistant with the study done by Aho M et al⁹, where they noted that heart rate following one minute post intubation had comparitive increase than the control group.

In group B (1 mcg/kg) after administring the study drug, there was a fall in heart rate from the baseline till induction and was statistically highly significant. During intubation and one minute post intubation there was rise in heart rate minimally from the post induction value and thereafter it decreased. High statistical significance was however noted till 10 minutes post intubation from the baseline value. It attenuated the hemodynamic stress response of laryngoscopy and intubation but the fall in heart rate was comparitively more than group A (0.6 mcg/kg).

This result was similar to the study done by Basar et al who also noted that there was a continuous fall in heart rate even after laryngoscopy and intubation.

In group A after administrating the study drug, there was a fall in systolic blood pressure from the baseline which was statistically highly significant till induction. The systolic blood pressure during and one minute post intubation showed increase in value from the post induction but not more than the baseline value. But significant fall in SBP was noted from baseline till 10 minutes post intubation.

Scheinin et al¹⁰ observed that there was continuous fall in SBP till induction and minimal increase after intubation but not more than baseline value similar to our study.

In group B after administrating the study drug, there was a fall in systolic blood pressure from the baseline which was statistically highly significant till induction. During and post intubation also there was a continuous fall from baseline which was statistically highly significant. It attenuated the hemodynamic stress response of laryngoscopy and intubation and the fall in systolic blood pressure was comparitively more than group A.

In group A the baseline value was 126.70 +12.07 mm Hg and the fall in SBP was noted as 118.03 16.65 mm Hg at the time of intubation and 119.80+ 12.92 mm Hg at one minute post intubation. But in group B there was a significant drop in SBP from the baseline value 127.586.33 mm Hg to 111.58 + 15.30 mm Hg at the time of intubation and 111.13 10.06 mm Hg one minute post intubation, which showed highly statistically significant with p value < 0.05

Our study result resembled Menda et al¹¹ studies who observed the significant fall in SBP throughout study from the baseline in a similar manner. They divided the 30 patients into two groups as placebo and Dexmedetomidine group, gave 100ml of saline and Imcg/kg Dexmedetomidine in 100m of saline respectively.

In group A there was a fall in diastolic blood pressure from the baseline after administrating the study drug till induction. The DBP showed an increase more than the induction value but not more than the baseline value at the time of intubation and post intubation after one minute. The range of increase was 8 mmHg from induction value but not more than baseline value and there was a significant difference in the diastolic blood pressure from baseline till 10 minutes post intubation. It attenuates the hemodynamic response of laryngoscopy and intubation adequately.

This is similar to the study done by Jaakola et al¹², they also observed that there was continuous fall in DBP till induction but minimal increase after intubation compare to post induction value but less than basal value..

In group B after administrating the study drug there was a fall in diastolic blood pressure from the baseline which was statistically highly significant till 10 minutes post intubation. It attenuated the hemodynamic stress response of laryngoscopy and intubation but the fall in diastolic blood pressure was comparitively more than group A.

Menda et al¹¹ also observed that there was a continuous fall in DBP even after intubation similar to our study group.

In group A after administrating the study drug, there was a significant fall in mean arterial pressure from the baseline till induction. At the time of intubation and 1 minute post intubation the mean arterial pressure increased more than the induction value but not more than the baseline value. The range of increase was 9 mmHg from induction value but still less than baseline value. After that there was a significant fall in the diastolic blood pressure from baseline till 10 minutes after intubation which attenuates the hemodynamic response of laryngoscopy and intubation adequately.

In group B there was highly significant fall in MAP from baseline throughout the study except 5th minute after administrating the study drug. A study done by Menda et al on Dexmedetomidine also concludes the same results like there was a reduction in MAP from the baseline throughout the study.

There was significant fall in SpO, in both groups during the infusion of the study drug but post induction the SpO2 increased significantly because of pre oxygenation process. The statistical value was also highly significant. In both groups, there was a marked reduction in dose requirement of Thiopentone for induction comparative to normal patients.

In our study, 3 patients in each group developed hypotension which required pharmacological management and I patient in group A developed bradycardia which required pharmacological management.

Both doses of Dexmedetomidine (0.6mcg/kg & 1mcg/kg) attenuated the stress response of laryngoscopy and intubation effectively. The reduction in heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure was more in 1mcg/kg group. Hence Dexmedetomidine at a dose of 0.6mcg/kg itself is adequate to control the stress response of laryngoscopy and intubation

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