A randomized double blind study to evaluate the effect of nebulized dexmedetomidine on the haemodynamic response to laryngoscopy – Intubation and intubation conditions

Introduction

Following the introduction of anaesthesia, direct laryngoscopy and tracheal intubation are linked to hemodynamic alterations brought on by increased sympatho-adrenal activity, which may cause hypertension and/or tachycardia. In the vulnerable group, the effects of laryngoscopy and intubation may lead to ischemia, arrhythmias, cerebrovascular stroke, pulmonary edema, and an increase in intracranial pressure.1 Numerous medications, including as local anesthetics, beta-blockers, calcium channel blockers, and narcotic analgesics, have been used with varying degrees of efficacy to reduce the laryngoscopy and intubation response.1

A selective alpha 2 adreno receptor agonist with short acting, sedative, hypnotic, anxiolytic, sympatholytic, analgesic, and antisialogogue effects is dexmedetomidine. It encourages neurological, respiratory, and cardiac stability. It has eight times more alpha 2 and less alpha 1 receptor selectivity. Its activity lasts less time than clonidine.2 Additionally, it reduces the need for analgesics and anesthetics during surgery.3 Theoretically, because of these qualities, it might be used as a component of an anesthetic regimen. Due to its pleiotropic properties, its use in the perioperative period is rising.4

Dexmedetomidine has been tested to reduce the haemodynamic response to laryngoscopy and intubation via intravenous,5 intranasal,6 and oral7 routes. Inhaling dexmedetomidine may be a novel, non-invasive approach that shows promise. Following nebulization, the bioavailability of dexmedetomidine is 65% and 85% across the nasal and buccal mucosa, respectively.7 Since the drug is deposited after nebulization over the nasal, buccal, and respiratory mucosa, nebulized dexmedetomidine may present an alluring option to both intravenous and intranasal modes of administration.8

Materials and Methods

This prospective, randomized, placebo-controlled, double-blind study was conducted, following approval from the Institutional Research Committee and Ethics Committee. The study spanned from December 1, 2020, to September 30, 2022, and involved ASA I and II adult patients aged 18 to 60, of either gender, scheduled for elective surgeries requiring tracheal intubation and general anesthesia. Prior to participation, all individuals provided informed consent and were subsequently divided into two groups, with 50 participants in each group. Group P received a nebulization of 0.9% saline (4 ml) 30 minutes before the induction of anesthesia, while Group D received a nebulization of 1 ug/kg of dexmedetomidine diluted in 0.9% saline, also 30 minutes before anesthesia induction.

Inclusion criteria encompassed patients with ASA I & II, either gender, adults between 18 and 60 years, and Mallampati Score (MPS) I & II. Exclusion criteria included patients undergoing emergency surgeries, those with a body mass index exceeding 30 kg/m², individuals with known or unanticipated difficult intubation, requiring more than 30 seconds or two attempts at laryngoscopy by a senior anesthesiologist, patients with rhythms other than sinus, those on anti-hypertensive medications or beta blockers, individuals with a known allergy to dexmedetomidine, and those on preoperative drugs that could potentially confound the study (clonidine, gabapentin, pregabalin, steroids). Cardiac surgeries were also excluded from the study. Preoperative preparations included pre-anaesthetic checkup, obtaining informed consent, fasting for at least 6 hours, and administration of medication as prescribed.

During the surgery, patients were monitored and received nebulization as per their assigned group. After pre-oxygenation, anesthesia was induced, and intubation was performed. Intubation conditions were assessed using the Helbo-Hansen score (Steyn’s modifications), and patients were monitored for any adverse events or complications. Post-surgery, patients were extubated and monitored in the postoperative care unit before being transferred to the ward upon meeting discharge criteria.

Result

A total of 100 patients posted for elective surgeries requiring general anaesthesia and tracheal intubation were divided into two different groups- Group D and Group P (based on randomization 1:1), each group including 50 patients. Data was described in terms of range; mean ±standard deviation (± SD), frequencies (number of cases) and relative frequencies (percentages) as appropriate. Comparison of quantitative variables between the groups were done using Student t-test and Mann Whitney test for parametric and non-parametric respectively. For comparing categorical data, Chi square (χ2) test was performed and exact test is used when the expected frequency is less than 5. A probability value (p value) less than 0.05 was considered statistically significant. All statistical calculations were done using (Statistical Package for the Social Science) SPSS 21version (SPSS Inc., Chicago, IL, USA) statistical program for Microsoft Windows.

Mean Heart rate at different intervals

The mean heart rate (HR) was assessed in both Group D and Group P. The findings revealed a significant reduction in heart rate in Group D compared to Group P at various time points. Specifically, there was a significant attenuation of HR in Group D at the time of laryngoscopy (p=0.007), 1 minute after intubation (p=0.001), 3 minutes after intubation (p=0.001), 5 minutes after intubation (p=0.001), 7 minutes after intubation (p=0.004), and 10 minutes after intubation (p=0.004). These results indicate a notable impact of the intervention in Group D on heart rate compared to the control group, Group P, at various time intervals during the study. (Figure 1)

Figure 1

Mean Heart rate at different intervals

Mean systolic BP at different intervals

The study revealed a significant reduction in the mean systolic blood pressure (SBP) in Group D compared to Group P at various time points. Specifically, there was a significant attenuation of mean SBP in Group D at the time of laryngoscopy (p=0.001), 1 minute after intubation (p=0.001), 3 minutes after intubation (p=0.001), 5 minutes after intubation (p=0.001), 7 minutes after intubation (p=0.001), and 10 minutes after intubation (p=0.001). These findings indicate a substantial impact of the intervention in Group D on systolic blood pressure compared to the control group, Group P, at various time intervals during the study. (Figure 2)

Figure 2

Mean systolic BP at different intervals

Mean diastolic BP at different intervals

The study demonstrated a significant reduction in the mean diastolic blood pressure (DBP) in Group D compared to Group P at various time points. Specifically, there was a significant decrease in mean DBP in Group D at the time of laryngoscopy (p=0.001), 1 minute after intubation (p=0.001), 3 minutes after intubation (p=0.001), 5 minutes after intubation (p=0.001), and 10 minutes after intubation (p=0.001). However, it's worth noting that there was a less significant reduction in mean DBP at 7 minutes after intubation (p=0.047) in Group D. These results indicate a substantial impact of the intervention in Group D on diastolic blood pressure compared to the control group, Group P, at various time intervals during the study, with the most pronounced effect observed in the earlier time points. (Figure 3)

Figure 3

Mean diastolic BP at different intervals

Mean arterial pressure at different intervals

The study findings indicate that there were no statistically significant differences in the Mean Arterial Pressure (MAP) values measured at baseline (p=0.144) and after nebulization (p=0.114) between Group D and Group P. However, it's important to note that the mean MAP was significantly lower in Group D compared to Group P at various time points, including at the time of laryngoscopy (p=0.001), 1 minute after intubation (p=0.001), 3 minutes after intubation (p=0.001), 5 minutes after intubation (p=0.001), 7 minutes after intubation (p=0.001), and 10 minutes after intubation (p=0.001). These results suggest that while there were no baseline or post-nebulization differences in MAP between the groups, the intervention in Group D had a significant impact on reducing MAP at different time intervals during the study when compared to Group P. (Figure 4)

Figure 4

Mean arterial pessure at different intervals

Mean rate pressure product (RPP) at different intervals

The study results indicate that there were no statistically significant differences in the mean Rate Pressure Product (RPP) values measured at baseline (p=0.974) and after nebulization (p=0.111) between the Dexmedetomidine and Placebo groups. However, significant differences were observed at various time points during the study, including at the time of laryngoscopy (p=0.001), 1 minute after intubation (p=0.001), 3 minutes after intubation (p=0.001), 5 minutes after intubation (p=0.001), 7 minutes after intubation (p=0.001), and 10 minutes after intubation (p=0.001). These findings suggest that while there were no differences in RPP at baseline or after nebulization, significant variations were observed between the groups at different time intervals, particularly during and after intubation. (Figure 5)

Figure 5

Mean RPP at different intervals

Effect on intubation conditions

In the study, the assessment of intubation conditions revealed that 61% of the patients exhibited excellent intubation conditions, characterized by easy laryngoscopy, open vocal cords, absence of coughing, complete jaw relaxation, and no limb movements as per Steyn's modification of Helbo-Hansen score⁹. Additionally, 39% of the patients demonstrated good intubation conditions according to the same scoring system.

In Group D, 74.0% of the patients showed excellent intubation conditions, while 26% of them displayed good intubation conditions. In contrast, in Group P, 48% of the patients fell into the category of excellent intubation conditions, while 52% had good intubation conditions. The statistical analysis revealed a significant difference between the two groups, with a p-value of 0.013 and a chi-square value of 7.104. These findings suggest that the use of dexmedetomidine in Group D was associated with a higher proportion of patients exhibiting excellent intubation conditions compared to the control group, Group P. (Figure 6)

Figure 6

Distribution of patients according to intubation conditions

Incidence of side effects

Only 2% of the patients in each group experienced side effects, specifically sore throat. Notably, the vast majority of patients in both Group D and Group P, accounting for 98%, did not report any side effects, including symptoms like nausea, vomiting, dryness of the nose, headache, bradycardia, hypotension, or sore throat.

The statistical analysis demonstrated a chi-square value of 0.000, and the result was found to be statistically insignificant, with a p-value of 1.000. These results indicate that the occurrence of side effects, such as sore throat, was very low in both groups, and there were no statistically significant differences between the groups in terms of side effects. (Figure 7)

Figure 7

Distribution of patients according to side effects

Discussion

Endotracheal intubation and laryngoscopy are unpleasant stimuli that can cause a wide range of stress reactions, including tachycardia, hypertension, bronchospasm, laryngospasm, increased intracranial pressure, and increased intraocular pressure.9 Patients with cardiovascular and cerebrovascular disorders may find increased cardiovascular reflexes to be harmful. During the administration of general anesthesia, avoiding the rise in sympathoadrenergic activity brought on by endotracheal intubation becomes crucial. Anaesthesiologists have experimented with a number of medications and innovative techniques to lessen patients' stress reactions during laryngoscopy and endotracheal intubation. The effectiveness of Dexmedetomidine at reducing the cardiovascular response to endotracheal intubation and providing better intubating conditions were to be assessed in the current study.

In our study, there was an increase in heart rate from baseline in both the groups after laryngoscopy and intubation, but the increase in heart rate was highly significant in group P (placebo) at the time of laryngoscopy, 1 min, 3 min, 5 min, 7 min and 10 minutes after intubation and was insignificant in group D(dexmedetomidine) at similar intervals. Similar to the study done by Misra S. et al, 10 who assessed the effects of preoperative dexmedetomidine nebulization on the hemodynamic response to laryngoscopy and intubation, we noticed a considerable reduction of the increase in heart rate in group D. Additionally, we noticed a decrease in perioperative opioid and anesthetic drug use.

In our study found that there was significant attenuation of SBP and DBP and MAP at 1 min, 5 min, and 10 min following intubation in the group of patients who received dexmedetomidine nebulization (1 µg/kg). Shrivastava P et al11 observed there was a statistically significant difference in the SBP of the two groups (control and dexmedetomidine) recorded before laryngoscopy (p = 0.019), after intubation (p = 0.007), after one minute of intubation (p < 0.001), after five minutes (p < 0.001), and after 10 minutes (p = 0.010) of intubation which was similar to our study and the difference in mean DBP at time intervals before laryngoscopy (p < 0.001), after intubation (p = 0.034), after one minute (p = 0.011), after five minutes (p <0.005), and after 10 minutes (p = 0.009) of intubation when compared between the control and study groups; however, at baseline, no significant difference was observed between the two groups (p = 0.201). The significant difference in the MAP at time intervals before laryngoscopy (p< 0.047), after intubation (p = 0.042), after one minute (p = 0.001), after five minutes (p < 0.006), and after 10minutes (p = 0.018) of intubation when compared between the control and study groups which was similar to our study.

Singh V13 et al. evaluated the effects of nebulized dexmedetomidine (1 g/kg in 3-4 ml of 0.9% saline) and intravenous (1 g/kg over 10 min) dexmedetomidine on attenuating the stress response to laryngoscopy and intubation. The rate-pressure product in their trial never reached the critical ischemia value of 12000 in either group, which is comparable to our findings and makes nebulized dexmedetomidine a feasible alternative for individuals who are poor candidates for hypo- or hypertension or Brady/tachycardia. In our study Group D showed better control on RPP than group P and it showed a better control of haemodynamics with nebulized dexmedetomidine. This showed cardioprotective effect of dexmedetomidine which leads to a reduction in perioperative myocardial ischemia episodes.

The study done by Gu W et al 12 observed the incidence and severity of coughing, condition of vocal cords, jaw relaxation and limb movements in patients for flexible bronchoscopy. They discovered that 15% of people receiving nebulized dexmedetomidine, 50% of people receiving intravenous dexmedetomidine, and 55% of people receiving nebulized lidocaine experienced moderate to severe coughing. In our study we used steyn’s modification of Halbo-Hansen scoring 13 to evaluate the intubation conditions. We observed that the nebulized dexmedetomidine significantly facilitate the intubation conditions like easy laryngoscopy, open vocal cords, no coughing, complete jaw relaxation, and no limb movements and it showed a significant difference as compared to saline nebulization. Nebulized dexmedetomidine in their study shown a protective benefit for lowering coughing in comparison to intravenous dexmedetomidine, with the nebulized dexmedetomidine group having the lowest incidence of moderate to severe coughing (P=0.019). Nimmagadda et al.'s 14 evaluation of nebulized dexmedetomidine as a premedication to blunt hemodynamic response to laryngoscopy and tracheal intubation without bradycardia or hypotension was comparable to our study's findings that dexmedetomidine blunts stress response without any side effects. In our study we observed for perioperative hypotension, bradycardia and post-operative dryness of nose, nausea, vomiting, sore throat and headache. Only 2% patients showed side effects (sore throat) in each group. In both group D and group P 98% patients never showed any side effects. The chi square value was 0.000 and result was statistically insignificant (p value 1.000). Commonly seen haemodynamic instability associated with Dexmedetomidine was not seen in our study, this may be because of lower dose and nebulized route of administration.

Our study had some limitations. It was conducted in ASA 1 and ASA 2 status patients while the population who can most benefit from the study probably belong to ASA 3 and 4. It was decided not to include them in the study course due to ethical considerations.

Conclusion

In conclusion, our study demonstrated that nebulizing dexmedetomidine at a dose of 1 mcg/kg effectively reduces the hemodynamic response to laryngoscopy and intubation without elevating the risk of hypotension or bradycardia. Dexmedetomidine provided more stable heart rate and mean arterial pressure compared to the control group. Moreover, the intubation conditions were excellent following dexmedetomidine nebulization. This novel method of administration shows promise in mitigating the hemodynamic response to laryngoscopy and intubation.

Further research in this area is warranted, as preoperative nebulization of dexmedetomidine appears to be a potential intervention for minimizing the hemodynamic response to laryngoscopy and intubation while enhancing intubation conditions. Importantly, patients in both groups, whether receiving dexmedetomidine or a placebo, did not experience any adverse effects. Preoperative nebulization with dexmedetomidine may prove to be an effective strategy for reducing the hemodynamic response to intubation, improving intubation conditions, and reducing intraoperative anesthetic and analgesic requirements without causing significant adverse effects.

Source of Funding

Nil.

Conflicts of Interest

There are no conflicts of interest.