Endotracheal intubation, a common procedure in surgical settings, is accompanied by a surge in sympathetic activity, giving rise to marked hemodynamic perturbations. These responses encompass elevations in blood pressure, heart rate, and myocardial oxygen demand, which can be of particular concern in patients with pre-existing cardiovascular conditions. Effective attenuation of these adverse cardiovascular effects during laryngoscopy and intubation is essential for preventing perioperative complications and ensuring optimal patient outcomes. [1].  Dexmedetomidine, an α2-adrenergic agonist with a high selectivity profile, has garnered attention for its multifaceted pharmacological properties, including sedation, anxiolysis, analgesia, and sympatholysis [2] . Operating through the modulation of norepinephrine release, dexmedetomidine acts centrally within the locus ceruleus, exerting inhibitory control over sympathetic outflow. This unique mechanism offers a potential solution to dampen the undesirable hemodynamic changes triggered by airway manipulation.[3] Within the realm of anesthesia, dexmedetomidine's role as an adjuvant has expanded due to its ability to mitigate the hemodynamic response associated with laryngoscopy and intubation.[4] By targeting the autonomic nervous system and blunting stressinduced sympathetic activation, dexmedetomidine emerges as a promising tool for enhancing perioperative cardiovascular stability. However, a critical aspect that remains under scrutiny is the determination of the optimal dexmedetomidine dosage. This issue assumes greater significance given the variability in drug responses among different populations. In the context of the Indian population, such variability may arise due to genetic, metabolic, or environmental factors. Therefore, elucidating the appropriate dexmedetomidine dose assumes heightened importance, particularly when considering the pharmacological management of perioperative hemodynamics in the Indian subset. The dearth of consensus on the ideal dexmedetomidine dosage underscores the need for rigorous investigation to establish evidence-based guidelines. In essence, the rationale for this study is grounded in the quest for precision medicine within anesthesia practice. Tailoring dexmedetomidine dosing to the Indian population subset can potentially confer benefits in terms of enhanced hemodynamic stability during the critical peri-intubation period. Given the growing recognition of dexmedetomidine as a versatile adjuvant, elucidating the most effective dose in this specific context holds considerable clinical relevance. Thus the present research investigation aims to assess the impact of varying doses (0.5 mcg/kg vs 1 mcg/kg) of dexmedetomidine on hemodynamic responses during laryngoscopy and endotracheal intubation while evaluating potential adverse effects.

This  was  a  randomized  double  blind  study conducted at Nepal Medical College and Teaching Hospital  from  June  to  August  2019.  Ethical approval from the Institutional Review Committee of Nepal Medical College and Teaching Hospital was obtained. Thorough pre-operative evaluation of the patients was done a day before surgery. A total of 60 patients, aged 18-55 years of either sex, ASA PS I and II posted for elective surgery under general  anesthesia  were  included  in  this  study. Patients with hypertension and cardiac disease, patients with difficult airway (Mallampatti Grade III  and  IV),  obese  patients  (BMI  >25),  patients with  endocrinal  diseases  like  hyperthyroidism and  hypothyroidism,  patients  allergic  to  the study drug, patients with baseline heart rate < 60 beats/minute and patients on beta blockers were excluded from the study. Those patients who had intubation  attempt  lasting  longer  than  15  sec, and  multiple  intubation  attempts  (2  or  more) were also excluded from the study. An informed written consent was obtained from all the patients who  meet  the  inclusion  criteria.  Premedication was done with tab. Lorazepam 2 mg for patients weighing  50  kg  or  more  and  tab.  Lorazepam  1 mg for patients weighing less than 50 kg on the night before surgery. The patients were kept nil per  oral  for  at  least  8  hours  for  solid  food  and sips of clear liquid were allowed till 2 hours prior to surgery. The patients were allocated into two groups: Group A and Group B, 30 patients in each group, by slips of paper in a box technique. One of the anesthesiologist prepared the intravenous infusion and coded them. The coded infusion was given to the resident anesthetist, who was unaware of its content, to be administered to the patients. The same resident was given the responsibility of monitoring the patient intraoperatively and recording all the hemodynamic parameters of the patients. All the intubations were done by the co-author of the study.In the operating room ECG, pulse oximeter and non-invasive  blood  pressure  (NIBP)  cuff  were attached.  Baseline cardiovascular parameters i.e. heart rate, blood pressure (systolic, diastolic and mean) and oxygen saturation were recorded. Intravenous (IV) access secured with appropriate sized cannula. Patients  belonging  to  the  Group A  (n=30)  received  dexmedetomidine  0.5  μg/kg diluted with 0.9% normal saline to make a total 20  ml  volume,  slowly  IV  over  10  minutes  via syringe pump. Patients belonging to the Group B (n=30) received dexmedetomidine 1 μg/kg diluted with 0.9% normal saline to make 20 ml volume, slowly  IV  over  10  minutes  via  syringe  pump. Vitals  heart  rate  (HR),  systolic  blood  pressure (SBP),  diastolic  blood  pressure  (DBP),  mean arterial  pressure  (MAP)  and  oxygen  saturation (SpO2)  were  monitored  during  infusion  of the  drug.  General  anesthesia  technique  was standardized  for  both  the  groups.  Inj.  Fentanyl 2  μg/kg  was  given,  induction  was  done  with Propofol 1% injection in incremental dose until loss of eyelash reflex was attained. Isoflurane at 0.5%  was  turned  on.  After  confirmation  of  bag and mask ventilation, vecuronium 0.1 mg/kg was given.  One  minute  after  vecuronium  injection, isoflurane  was  increased  to  2%  to  deepen  the anesthesia.  Three  minutes  after  vecuronium injection,  direct  laryngoscopy  and  intubation was done. Heart rate, systolic, diastolic and mean arterial pressure was recorded before giving the test drug, after completion of the administration of  the  test  drug  at  5  and  10  minutes,  after induction, after intubation at 1 minute, 2 minutes and  5  minutes.  Maintenance  of  anesthesia  was done   with   isoflurane,   oxygen,   vecuronium with IPPV and fentanyl as needed. At the end of the  surgery,  residual  effect  of  neuromuscular blockade  was  reversed  by  Neostigmine  2.5  mg and  glycopyrolate  0.4  mg.  Patients  were  then extubated  and  transferred  to  the  post-operative ward. The duration of surgery and the duration of anaesthesia were also recorded.Clinically relevant hypotension was defined as a decrease in systolic arterial blood pressure by 20% or more from baseline value. It was treated with 200 ml Ringer’s lactate solution. If ineffective, 5 mg mephentermine was given. Clinically relevant bradycardia  was  defined  as  heart  rate  <  50 Thapa et al beats/min and was treated with atropine 0.6 mg intravenously.Data were entered in Microsoft Excel and analyzed with the Statistical Package for the Social Science (SPSS). A p value < 0.05 was considered to indicate statistical significance in all tests

In our study both the groups were comparable with regard to demographic parameters like age and sex.

Table 1: Distribution of patients according to Age in percentage

There was decrease in the mean heart rate (HR) after administration of the study drug, throughout the study period in both the groups.

                Table 2: Comparison of Mean Heart Rate changes between Group A and Group B

S – Significant, HS – Highly Significant, NS – Non-Significant

As compared to the baseline mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP), mean blood pressure (MBP) was decreased in both the groups which continued throughout the study period.

Table 3: Comparison of mean Systolic Blood Pressure Changes between Group A and Group B

Table 4: Comparison of Mean Diastolic Blood Pressure Changes Group A and Group B

S – Significant, HS – Highly Significant, NS – Non-Significant

Group B showed more fall in the HR from 4^th minute of drug administration up to 10th min. At intubation, it showed slight rise in both the groups compared to pre induction value though actual value being less compared to the baseline (Group A: 78.70±3.84, - 9.79% vs. Group B: 74.57±4.14 percentage value -10.51%) (P value >0.05). The fall was also seen post intubation from 1 min up to 10 min, the difference in HR being statistically significant at 5 and 10min. Maximum fall in the HR was observed in both the groups post intubation at 10 minutes. Fall in heart rate was more in Group B than Group A. At induction, at intubation and post intubation at 1 min, the fall in all types of blood pressure was noted in both the groups. This fall in blood pressure is less as compared to baseline not requiring any treatment. Here also Group B showing more fall than Group A. Post intubation fall in SBP at 1min, and 5 min was statistically not significant. There was decrease in SBP in both the groups post intubation at 10 min which was statistically highly significant in Group B than in Group A. There was decrease in DBP in both the groups post intubation at 5 min and 10 min which was statistically highly significant.

At intubation and post intubation at 1 min, the fall in MBP was less as compared to the baseline in both the groups. Group B showing more fall than Group A. There was decrease in MBP in both the groups post intubation at 10 min which was statistically significant. Fall in mean blood pressure was more in Group B than in Group A. In Group A, one patient and in Group B, 2 patients had bradycardia (HR<50bpm) none of the patients in both the groups had hypotension (BP >30%) from the baseline.

Dexmedetomidine, an alpha-2 agonists drug has been tried for reducing the intubation response and found to have better effects compared to other drugs with reduced or no side effects like respiratory depression. When used intravenously it inhibits the release of nor-epinephrine by presynaptic activation of the α -2 adrenoceptor in the Locus coeruleus. Post synaptic activation of α -2 adrenoceptor in the central nervous system by this drug results in decrease in sympathetic activity. Its use decreases the serum catecholamine levels by 90% and suppresses the hemodynamic response of laryngoscopy. Dexmedetomidine decreases heart rate by augmenting the vagal nerve and blocking the cardio-accelerator nerves. This negative chronotropic effect is also attributed to reflex response for transient hypertension during initial part of infusion and subsequently it was due to diminished norepinephrine release and inhibition of central sympathetic outflow [7, 8] . In our study after administration of the study drug, we observed the similar effect i.e. decrease in the mean heart rate compared to the baseline in both the groups which continued throughout the study period. At intubation, mean heart rate showed slight rise in both the groups compared to pre induction value, though actual value was less than the baseline and the values were comparable in both the groups. Post intubation at 5 min and 10 min there was statistical significant difference noted in two group with group B showing more fall. Hasan A et al. 2016 [9] compared the dose of 0.6 μ g/kg versus 1μ g/kg and observed continuous decrease in the mean heart rate throughout the study period in both the groups. Raval D L et al. 2014 (8,29), They found in their study that the fall in mean HR in Group A (1.0 μ g/kg dexmedetomidine) was more as compared to Group B (0.5μ g/kg dexmedetomidine), during laryngoscopy and intubation, 1 min after intubation, 2 min after intubation and 5 min after intubation which was statistically highly significant (p0.05). Their findings were almost similar with our study. We noted bradycardia (HR< 50/min) in Group B (0.5 μ g/kg dexmedetomidine), and 2 cases of bradycardia (HR < 50/min) in Group C (1 μ g/kg dexmedetomidine), respectively. In our study, after administration of the study drug, there was decrease in SBP, DBP, MBP compared to the baseline in both the groups which continued throughout the study period. Reduction of tonic levels of sympathetic outflow and an augmentation of cardiac-vagal activity due to Dexmedetomidine can result in decrease in cardiac output which in turn causes decrease in blood pressure. At induction, at intubation and post intubation at 1 min, the fall in SBP, DBP, and MAP was less as compared to the baseline in both the groups. Group B showing more fall than Group A. Post intubation fall in SBP at 1min, and 5 min was comparable in both the groups. There was decrease in mean SBP, DBP, MBP in both the groups post intubation at 10 min which was statistically highly significant in Group B than in Group A. Smitha et al. 2014 [11] compared the effect of 0.5 μ g/kg, 1 μ g/kg of dexmedetomidine and normal saline. They had similar findings for SBP like our study. In a similar study done by A EsraSagı roglu et al. [12] they noted statistically highly significant difference between 1 μ g/kg (Group A) and (Group B) 0.5 μ g/kg. As compared to baseline SBP had increased in both the groups 60 sec after induction which is not matching with our study. It might be because of the difference in the induction agents and inhalational agents as we used Inj. Propofol instead of Inj. Thiopentone and Isoflurane as an inhalational agent. Rashmi et al. 2013 [13] compared the two different doses of Dexmedetomidine, 0.6μ g/kg and 1μ g/kg and control group of NS. As seen in our study they also found fall in DBP after the start of Dexmedetomidine. At 1 min post intubation they have noted the rise in DBP above the baseline in both Dexmedetomidine groups. We noted rise in diastolic pressure but it was not more than that of Baseline, Smitha et al. [11] noted that values of diastolic blood pressure were statistically lower at all intervals in 1 μ g/kg than 0.5 μ g/kg of dexmedetomidine including 1 min post intubation value. This change in this study may be attributed to use of different opioids (Fentanyl 1-2 mcg/kg for induction) Modh B. Dixitkumar et al. [14] observed fall in MBP in Group D1(1mcg/kg Dexmedetomidine) till induction (baseline vs. induction) which was less at 1 min (value)and 2 min (value) post intubation. This was like our Group B study. Rawal. D et al. [8] noticed fall in MBP in both the groups at all time intervals which was more in 1mcg/kg Dexmedetomidine compared to the baseline. At 1 min after intubation, less fall was noticed as compared to the baseline. This finding is unlike our study Jarineshin H [15] noticed fall in MBP from baseline after study drug infusion. At intubation and at 3 min post intubation there was less fall compared to the baseline. Their study findings were correlating our study. H S Nanda et al. 2016 [10] noticed fall in the MBP in Group B: 0.5 μ g/kg and Group C: 1 μ g/kg from the baseline after completion of the study drug. In Group B, there was slight rise in the MBP immediately after intubation, at 1min and it was above the baseline. At 3min the value matches the baseline. At 5 min and 10 min again fall was seen. In Group C, There was fall in mean blood pressure throughout the study period, Less fall was seen immediately after intubation and at 1 min post intubation and it was statistically highly significant as compared to Group B. These findings were found to be similar with our study. None of the patients in our study had hypotension. Our findings match with the study by Allam Hasan et al. and Nanda et al.

According to our study, inj. dexmedetomidine 0.75µg/kg provides statistically significant attenuation of hemodynamic response to laryngoscopy and endotracheal intubation as compared to inj. dexmedetomidine 0.5µg/kg without having significant adverse effects, with better hemodynamic stability along with dose sparing effect of propofol for induction.

Thus, from the present study, we conclude inj. dexmedetomidine 0.75µg/kg as more effective in attenuating the response to laryngoscopy and endotracheal intubation.

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