Stimulus incite following laryngoscopy and intubation shows remarkable sympathetic activity leading to a brief period of extreme hemodynamic and circulatory stress in patients undergoing major surgery under general anesthesia. These transitory changes may be harmful for some patients undergoing major surgery, specifically those patients who have predisposing factors like hypertension, left ventricular hypertrophy, myocardial ischemia, cerebrovascular diseases, cerebral haemorrhage. Different premedications are used to reduce anxiety, amnesia and for prevention of above stress response and to reduce anaesthetic requirements 

Dexmedetomidine is a highly selective, α2 adrenoreceptor agonist drug, which has sedative, analgesic and anxiolytic property without any respiratory depressive action. It is also a short acting drug with a terminal elimination half-life (t1/2β) of 2 hours. Dexmedetomidine causes post synaptic activation of α2 adrenoreceptors in the CNS resulting in hypotension and bradycardia through sympatholysis. Preoperative administration of dexmedetomidine can successfully attenuate the laryngoscopic stress response which can be used either by intravenous, intramuscular or intranasal routes.^1,2 Intranasal route is the most used extravascular route of administration of dexmedetomidine in practice.³ When comparing dexmedetomidine at a dose of 1 µg/kg body weight in one study between intravenous (i.v.) and intranasal route(i.n.) showed that onset time of sedation was 15 – 20 minutes through i.v. route and 30 –45 minutes through i.n. route.⁴ Also, dexmedetomidine when administered preoperatively, resulted in a decrease in induction dose of thiopentone by upto 30%.⁵

Aim: To determine whether intranasal administration of dexmedetomidine will attenuate the haemodynamic response to laryngoscopy and endotracheal intubation in the same way as intravenous Dexmedetomidine infusion.

Objective:  To compare the baseline  values  and  the  readings  thereafter  (after administration of study drug) of heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure between the two groups, i.e., the intravenous group D(IV) and the intranasal group D(IN) in the pre induction and the post intubation period. We will also compare for side effects if any, within the study period between the two groups.

This was a Hospital based observational study conducted by Department of Anaesthesiology, Assam Medical College and Hospital, Dibrugarh from June, 2021 to May, 2022 on the patients undergoing abdominal surgery under general anaesthesia in Assam Medical College & Hospital. Ethical clearance obtained from the Institutional Ethics Committee (Human) of Assam Medical College & Hospital.

Patient selection:

Inclusion criteria

1. All patients aged 18– 60 of either sex. ASA grade should be ASA Grade I and II (ASA Grade I - normal healthy patient, ASA Grade II - Patient with mild systemic disease).
2. Patients opting for elective abdominal surgery under general
3. Mallampati airway assessment of grade

Exclusion criteria

1. Patient refusal to participate in the study, known history of allergy or hypersensitivity for dexmedetomidine, suffered from significant cardiac and respiratory disease and predicted difficult airway were excluded from this
2. Patients on psychotropic
3. Neurosurgical cases having preoperative
4. Patients with neurological and other endocrine
5. Patients with renal impairment and hepatic
6. Patients with cardiovascular diseases, diabetes mellitus, asthma,
7. Patients on beta blockers or calcium channel blockers or rate regulating
8. Previous records of failed
9. Laryngoscopy and intubation time needing more than 15
10. Patients with nasal pathology like nasal polyp, deviated nasal septum, nasal

Study variables

• Noninvasive mean arterial pressure (MAP),
• Heart rate (HR)
• Systolic blood pressure
• Diastolic blood pressure

Sample size calculation: Eighty (80) patients Divided into two groups of 40 each. By taking 95% Confidence Interval, with 90% Power. Sample size for this present study is calculated and rounded off to be 40 in each of the two groups.

Sampling technique: Simple random sampling.

The groups were tested for homogeneity with respect to baseline heart rate, mean arterial pressure, systolic blood pressure and diastolic blood pressure. The groups were found to be homogenous with respect to these  hemodynamic parameter at 5% level of significance.

Table1-Comparison    of   pre   and      post    i nduction     heart     rate

The table shows, the baseline mean heart rate was statistically insignificant. A statistically significant difference (p < 0.05) in heart rate was seen between the two groups at 30 minutes (p-value – 0.024) and 40 minutes (p-value – 0.011) after the study drug administration. At laryngoscopy and intubation, heart rate rise was maximum seen in both the groups and the p-value was 0.004 and it was highly significant. The heart rate rise was more in D(IN) group. In post intubation period, the heart rate was statistically insignificant between the two groups. However, the heart rate rise was more in D(IN) group.

Table 2-Comparison of pre and post Induction systolic blood pressure

The table shows, that the baseline mean systolic blood pressure was statistically insignificant. In pre induction period, after the drug was given in both the groups, systolic blood pressure got lowered from the baseline values. And the maximum reduction in systolic blood pressure was observed at 40 minute time interval. The systolic blood pressure was slightly lower in the D(IV) group at all times as compared with the DIN group. However, systolic blood pressure difference between the two groups in intergroup comparison was statistically insignificant at all time intervals in the pre induction period.

During laryngoscopy and intubation procedure, there was rise in blood pressure in both the groups and the rise was more in group D(IN) but was not statistically significant.

Then, after the procedure of laryngoscopy and intubation, systolic blood pressure started decreasing gradually and systolic blood pressure was slightly higher in group D(IN) at all time intervals in the post intubation period during intergroup comparison. But the difference during intergroup comparison in post intubation time intervals was statistically insignificant (p-value > 0.05).

Table 3: Comparison of Pre and Post Induction diastolic Blood Pressure

The table shows the baseline mean diastolic blood pressure was statistically insignificant between the D(IV) and D(IN) group. Both the groups showed lowering of the diastolic blood pressure after administration of drug dexmedetomidine from the baseline values. And the maximum reduction was seen 40 minutes after the administration of the drug, but was statistically insignificant. The diastolic blood pressure was higher in all time intervals before intubation in group D(IV). However, in intergroup comparison, p-value was statistically insignificant.

Table 4: Comparison of Pre and Post

In this table, the baseline mean arterial pressure was statistically insignificant. The mean arterial pressure then decreased gradually after the drug administration from the baseline reading but it was statistically insignificant in all the pre induction time intervals. At laryngoscopy and intubation, the MAP increased in both groups and it was also statistically insignificant. Then it started decreasing gradually in post intubation period and it was statistically insignificant during the intergroup comparison in all time intervals in post intubation period.

In our present study, we have compared between the two routes of the drug dexmedetomidine, the i.v. route and the i.n. route to attenuate the hemodynamic response to L-I and to understand, whether i.v. route causes more changes in blood pressure and heart rate or the i.n. route or both routes cause similar suppression of blood pressure and heart rate.

Dexmedetomidine has been used in past years to overcome this stress response in different doses through i.v. route, intranasal route and i.m. route. Most researchers in their studies have taken the dose of dexmedetomidine in the range of 0.5-1.0 µg/kg of the body weight. We, in our study have taken the dose of dexmedetomidine as 0.5µg/kg of the body weight for i.v. route administration and 1.0 µg/kg of the body weight for intranasal route of administration in accordance with some of the studies listed below –

In a placebo controlled double blind study, Aantaa R et al. in 1990 used dexmedetomidine at a dose of 0.5 µg/kg body

weight i.v. to evaluate it’                                                                                                                                       s hemodynamic and anesthetic sparing effects in patients undergoing minor gynaecological surgeries.6

In an another placebo controlled double blind study, Jaakola ML et al. in 1992 used dexmedetomidine at 0.6µg/kg body weight to see it’s hemodynamic response, IOP reducing properties and anesthetic sparing properties in patients undergoing ophthalmic surgeries.⁷

Scheinin B et al. in 1992 used dexmedetomidine at a dose of 0.6 µg/kg body weight in a study to evaluate it’s haemodynamic suppression response towards laryngoscopy and intubation (L-I). ⁸

Jayaraman L et al. in 2013 conducted a study, to evaluate the effect of intranasal dexmedetomidine versus oral alprazolam as a premedication agent in morbidly obese patients undergoing bariatric surgery and used dexmedetomidine at a dose of 1.0 µg/kg of body weight.⁹

G Han et al. in 2014 conducted a study, randomized study of intranasal vs. intravenous infusion of dexmedetomidine in gastroscopy and used dexmedetomidine at a dose of 0.50 µg/kg body weight in both groups, the intravenous group and the intranasal group.¹⁰

Jain V et al. in 2015 conducted a study, comparison of dexmedetomidine and fentanyl for attenuation of the hemodynamic response to L-I at a dose of 1.0 µg/kg of body weight.¹¹

Miller’s Anesthesia says as a premedicant, dexmedetomidine at i.v. doses of 0.33 to 0.67 µg/kg body weight given 15 minutes before the surgical procedure, seems efficacious, while minimizing the cardiovascular side effects of hypotension and bradycardia. Dexmedetomidine has a high bioavailability when administered nasally or buccally. ¹²

Sebastian B et al. in 2017 conducted a study, attenuation of haemodynamic response to Laryngoscopy and intubation with i.v. dexmedetomidine : A comparison between two doses and used dexmedetomidine at a dose of 0.5 µg/kg and 0.75 µg/kg of body weight. ¹³

MP Singh et al. in 2018 conducted a study, comparative evaluation of intravenous dexmedetomidine and sublingual nitroglycerine spray to attenuate hemodynamic response to L-I and used dexmedetomidine at a dose of 0.5 µg/kg body weight. ¹⁴

Yadav DK et al. in 2018 conducted a study, a clinical comparative study of effect of intranasal dexmedetomidine and clonidine on hemodynamic response during laryngoscopy in hypertensive adult patients and gave dexmedetomidine at a dose of 1.0 µg/kg of body weight. ¹⁵

A Singh et al. in 2018 conducted a study, attenuation of the pressor response to L-I with i.v. dexmedetomidine versus magnesium sulphate under bispectral index controlled anaesthesia and used dexmedetomidine at a dose of 1.0 µg/kg of body weight. ¹⁶

Niyogi S et al. in 2019 conducted a study, comparison between intranasal and intravenous route in administration of dexmedetomidine to attenuate hemodynamic response to L-I in a dose of 0.5-1.0 µg/kg body weight. ¹⁷

Zhang L et al. in 2019 conducted a study, the effects of intranasal dexmedetomidine premedication on sedation and stress of tracheal intubation in patients undergone gynecological laparoscopic surgery and gave i.v. dexmedetomidine at a dose of 1.0 µg/kg of body weight. ¹⁸

In our present study, we used drug dexmedetomidine 0.50 μg/kg (diluted in 50 ml syringe with normal saline) through an infusion pump over 40 minutes before induction in group D(IV) and in group D(IN), we used the same drug through intranasal route at a dose of 1 μg/kg in undiluted form in both the nostrils 40 minutes before the induction. From the above discussion, the dose of dexmedetomidine through both the routes seems to be optimal and justified.

PRE INDUCTION PERIOD:

In our study, the baseline values of the observed parameters (at zero time interval) like heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and the mean arterial pressure (MAP) for both the groups were statistically insignificant and so were comparable in their baseline characteristics. After the administration of study drug, there was a fall in the values of all the parameters in both the groups, i.e., Group D(IV) and Group D(IN).

The mean baseline heart rate in group D(IV)was 82.73 ± 5.95 per min and it decreased to 80.33 ± 5.93 per min at 10 minutes time interval. Similarly, mean baseline heart rate in group D(IN)was 85.13 ± 5.21 per min and it decreased to 82.30 ± 5.23 per min at 10 minute interval, i.e., 10 minutes after the drug administration. The p-value came out to be 0.118 and so was statistically insignificant. The p-value at 20 minute time interval was also statistically insignificant (0.081). The p-value became statistically significant at 30 and 40 minute time interval in pre induction period. The p-value at 30 minute time interval was 0.024 and at 40 minute time interval was 0.011.

Similarly, the basal systolic blood pressure in group D(IV) was 126.85 ± 9.67 mmHg and in group D(IN)was 127.65 ± 4.57 mmHg and after administration of the drug in both the groups, it started decreasing. The readings were taken at 10, 20, 30 and 40 minute time interval between the two groups but during comparison, the p-value was statistically insignificant. The systolic blood pressure was slightly lower in group D(IV) as compared to group D(IN)at all time intervals in the pre induction period.

In comparison of diastolic blood pressure between the two groups, basal reading in group D(IV) was 82.58 ± 4.87 mmHg and in group D(IN)was 83.15 ± 5.27 mmHg. It decreased gradually after the administration of the drug dexmedetomidine in both the groups but in intergroup comparison at 10, 20, 30 and 40 minute time interval, p-value was statistically insignificant. The diastolic blood pressure was slightly higher in all time intervals before intubation in group D(IV) as compared to group DIN.

In comparison of mean arterial pressure between the two groups, basal reading in group D(IV) was 97.33 ± 4.96 mmHg and in group D(IN)was 97.98 ± 3.56 mmHg. After administration of drug dexmedetomidine, there was fall in mean arterial pressure in both the groups, but the p-value was not significant in any of the time intervals in the pre induction period.

INDUCTION PERIOD:

In the present study, we found that maximum fall in haemodynamic parameters were seen in the induction period. The heart rate decreased further during the induction period in the two groups. In group D(IV), it was 67.43±5.45 beats/minute and in group D(IN)was 69.00±5.00 beats/minute. The p-value came out to be 0.118 which was statistically insignificant.

The systolic blood pressure in the two groups at induction interval was 110.90 ± 7.01 mmHg in group D (IV) and in group D(IN)was 111.00 ± 4.51 mmHg. The p-value during intergroup comparison came out to be 0.939 which was not statistically significant.

The diastolic blood pressure also reduced further in the induction period and it was measured as 69.93 ± 3.86 mmHg in group D(IV) and in group DIN, it was 68.60 ± 4.06 mmHg. The p-value came out to be 0.138 which was not statistically significant)

The mean arterial pressure when compared between the two groups at induction interval was 83.58 ± 3.85 mmHg in group D(IV) and 82.73 ± 3.16 in group D(IN). The p-value came out to be 0.284 which was not statistically significant.

DURING LARYNGOSCOPY AND INTUBATION:

Laryngoscopy and intubation are the main stressful events which cause tachycardia and hypertension. In our study, the maximum rise in heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure was seen in this time interval only. Mean heart rate was 87.18±5.54 beats/minute in group D(IV) and 90.95±6.02 beats/minute in group DIN. The p-value in intergroup comparison came out to be 0.004 which was statistically significant.

The systolic blood pressure also increased following laryngoscopy and intubation and was measured as 123.68 ± 7.04 mmHg in group D(IV) and 126.15 ± 4.51 mmHg in group DIN. The p-value came out to be 0.064 which was not statistically significant.

Similarly, the diastolic blood pressure also increased and came out to be 81.03 ± 4.32 mmHg in group D(IV) and 82.03 ± 3.78 mmHg in group DIN. The p-value when compared in intergroup comparison came out to be 0.274 which was statistically insignificant.

Similarly, the mean arterial pressure also increased in laryngoscopy and intubation interval and came out to be 95.24 ± 4.08 mmHg in group D(IV) and 96.73 ± 2.96 mmHg in group DIN. The p-value came out to be 0.064 in intergroup comparison which was not statistically significant.

POST LARYNGOSCOPY AND INTUBATION:

In the present study, we observed that the heart rate in group D(IV) at one minute post laryngoscopy and intubation time interval increased and came out to be 88.30 ± 5.23 beats/ minute and in group D(IN), it decreased and came out to be 88.85 ± 6.07 beats/ minute. The p-value was 0.665 which was not statistically significant. The heart rate then further reduced in both the groups, however, it was slightly higher in group D(IN)but when compared between the two groups, it was not statistically significant at any time interval post induction. The readings were taken at one minute post induction time interval, then two minute, three minute, four minute, five minute, seven minute and at ten minute time interval. We saw in both the groups that the value of heart rate started returning to near baseline at ten minute time interval post laryngoscopy and intubation.

The systolic blood pressure when measured at one minute time interval in post induction period, came out to be 124.65 ± 7.08 mmHg in group D(IV), and in group DIN, it came to be 126.08 mmHg. The p-value measured was 0.300 which was not statistically significant. The systolic blood pressure at subsequent further time intervals decreased in both the groups. The systolic blood pressure was slightly higher in group D(IN)when compared with group D(IV) at 2, 3, 4, 5 and 7 minute time interval following laryngoscopy and intubation. But during intergroup comparison, the p-value was not statistically significant in any of the time intervals post induction.

The diastolic blood pressure when measured at one minute time interval in post induction period was 80.35 ± 3.80 mmHg in group D(IV) and in group D(IN)was 80.70± 3.93 mmHg. The diastolic blood pressure decreased in both the groups when compared with the values of the laryngoscopy and intubation interval. The p-value at one minute time interval post induction was 0.686 which was not statistically significant. The diastolic blood pressure reduced further in both the groups in subsequent time intervals post induction. But the p-value in intergroup comparison in any of the time interval post induction was statistically not significant.

The mean arterial pressure at one minute time interval post induction was 95.12 ± 3.84 mmHg in group D(IV) and in group D(IN)was 95.83 ± 3.26 mmHg. The p-value came out to be 0.37 which was statistically not significant. The mean arterial pressure in subsequent time intervals reduced further in both the groups but in intergroup comparison, the p-value came out to be statistically insignificant.

From our study, we found that when drug dexmedetomidine given through intravenous route as an infusion (diluted in 50 ml of normal saline) or through intranasal route (in undiluted form), 40 minutes before the laryngoscopy and intubation procedure in patients undergoing elective major surgeries under general anaesthesia, cause similar response of attenuation of haemodynamic stress response to laryngoscopy and intubation. The haemodynamic parameters like heart rate, systolic blood pressure, diastolic blood pressure and mean blood pressure – all get lowered from their initial baseline values but all parameters are maintained within normal limits in both the groups, (Group D(IV) and Group DIN). The changes in heart rate and blood pressure are well controlled in our study in both the groups after administration of the drug dexmedetomidine at a dose of 0.5µg/kg in Group D(IV) and 1µg/kg in Group DIN. But we should be watchful for bradycardia and hypotension as the side effects. Thus, we can conclude that intranasal administration of dexmedetomidine drug will attenuate the haemodynamic stress response to laryngoscopy and endotracheal intubation in the same way as intravenous dexmedetomidine infusion.

1. Sun Y, Liu C, Zhang Y, Luo B, She S, Xu L, Ruan Low-dose intramuscular dexmedetomidine as premedication: a randomized controlled trial. Medical science monitor: international medical journal of experimental and clinical research. 2014;20: 2714.
2. Prabhu MK, Mehandale Comparison of oral dexmedetomidine versus oral midazolam as premedication to prevent emergence agitation after sevoflurane anaesthesia in paediatric patients. Indian Journal of Anaesthesia. 2017 Feb;61(2):131.
3. Li BL, Zhang N, Huang JX, Qiu QQ, Tian H, Ni J, Song XR, Yuen VM, Irwin A comparison of intranasal dexmedetomidine for sedation in children administered either by atomiser or by drops. Anaesthesia. 2016 May;71(5):522.
4. Zhang X, Bai X, Zhang Q, Lu The safety and efficacy of intranasal dexmedetomidine during electrochemotherapy for facial vascular malformation: a double-blind, randomized clinical trial. J Oral Maxillofac Surg. 2013 Nov;71(11):1835– 42.
5. Yabeck-Karam VG, Aouad Perioperative uses of dexmedetomidine. Middle East Journal of Anesthesiology. 2006 Oct 1;18(6):1043.
6. Aantaa R, Kanto J, Scheinin M, Kallio A, Scheinin Dexmedetomidine, an α2- adrenoceptor agonist, reduces anesthetic requirements for patients undergoing minor gynecologic surgery. Anesthesiology. 1990;73(2):230– 5.
7. Jaakola M, Ali-Melkkilä T, Kanto J, Kallio A, Scheinin H, Scheinin Dexmedetomidine reduces intraocular pressure, intubation responses and anaesthetic requirements in patients undergoing ophthalmic surgery. Br J Anaesth. 1992;68(6):570– 5.
8. Scheinin B, Lindgren L, Randell T, Scheinin H, Scheinin M. Dexmedetomidine attenuates sympathoadrenal responses to tracheal intubation and reduces the need for thiopentone and peroperative British journal of anaesthesia. 1992 Feb 1;68(2):126-31.
9. Jayaraman L, Sinha A, Punhani A comparative study to evaluate the effect of intranasal dexmedetomidine versus oral alprazolam as a premedication agent in morbidly obese patients undergoing bariatric surgery. J Anaesthesiol Clin Pharmacol. 2013;29(2):179– 82.

Han G, Yu WW, Zhao P. A randomized study of intranasal vs. intravenous infusion of dexmedetomidine in gastroscopy. International journal of clinical pharmacology and therapeutics. 2014 Sep 1;52(9):756-61