European Journal of Cardiovascular Medicine

General anaesthesia is a procedure to render a patient unconscious medically using certain drugs so as to perform surgeries without the patient feeling pain or being aware of the procedure [1]. General anaesthesia induction using endotracheal intubation leads to significant stress response. This response includes a spectrum of physiological changes such as increased catecholamines leading to increased blood pressure (BP), tachycardia or sometimes in severe cases, arrhythmias [2]. In patients with pre-existing cardiovascular pathology, these fluctuations could prove to be particularly detrimental [3]. Therefore, the attenuation of this stress response is a critical objective in anaesthetic management.

Opioids, particularly fentanyl, have been a mainstay in this context due to their potent analgesic and sympatholytic properties [4]. Fentanyl is an opioid analgesic which is commonly used as a preanesthetic medication to stabilise the cardiovascular parameters for laryngoscopy and intubation as well as during the operative procedure [4]. The effective clinical dose of fentanyl starts at 2 µg/kg. However, opioids carry risks of respiratory depression and their efficacy in completely blunting the stress response can be inconsistent [5].

Dexmedetomidine has emerged as a potential alternative to fentanyl for facilitating laryngoscopy and intubation. It is an α-receptor agonist, which has sympatholytic, analgesic and sedative activities without causing significant respiratory depression [6]. Additionally, dexmedetomidine has been shown to provide stable haemodynamic conditions and reduce perioperative stress responses. Out of the available doses of dexmedetomidine, 1 µg/kg dose has been found to be more effective in previous studies [6].

This study aimed to compare the effectiveness of intravenous fentanyl vs intravenous dexmedetomidine in reducing the stress response to laryngoscopy and endotracheal intubation in patients undergoing general anaesthesia. By evaluating hemodynamic parameters, objective of the study was to determine which drug offered a superior profile in managing the physiological stress associated with these procedures. This will help in potentially guiding the selection of agents to optimize patient outcomes and minimize perioperative risks related to anaesthetic practices.

A prospective study was conducted at the Department of Anaesthesiology at a tertiary care hospital in western India for a duration of one year. Approval of institutional ethics committee was obtained. Patients aged between 18 to 60 years admitted for surgery under general anaesthesia with American Society of Anaesthesiologists (ASA) grades I and II were enrolled for the study. Written informed consent was obtained from the patients after explaining the study procedure. Patients with hypertension with BP more than 140/90 mm Hg, hypotension with mean arterial pressure (MAP) below 80 mm Hg, bradycardia with heart rate (HR) below 50 beats per min (bpm), ischaemic heart disease, electrocardiogram (ECG) abnormalities, obesity with body mass index > 30 kg/m², bronchial asthma, endocrine diseases, liver and renal diseases were excluded. Also, patients with predicted difficult intubation, multiple laryngoscopy and intubation attempts, or requiring more than 30 seconds for intubation were also excluded from the study. Pregnant and lactating females were also not enrolled.  

Study Procedure:

Patients were enrolled using simple random sampling. The patients on the list of routine surgery under general anaesthesia were separated into two groups based on odd (group I) and even dates of surgery (group II). All patients had a comprehensive pre-anaesthesia evaluation that included a detailed history and clinical examination. Routine blood tests such as complete blood count, random blood sugar, serum creatinine and blood urea were done for all the patients. ECG and chest X-ray were also performed as a part of pre-anaesthetic work up.  Airway assessment was done using Mallampati classification.

The patients were kept nil by mouth for six hours before their surgery. Before starting the procedure, baseline HR, MAP, systolic and diastolic BP and SpO₂. Intravenous (IV) line was secured with 18-gauge IV cannula. All patients were premedicated with intravenous injections of glycopyrrolate (0.005-0.01 mg/kg), midazolam (0.02 mg/kg), ondansetron (0.1 mg/kg) and tramadol (2 mg/kg) 10 minutes before induction. In the operation theatre, vitals were again recorded by attaching pulse oximetry, ECG and non-invasive BP monitors. Patients in group I received 1 µg/kg Dexmedetomidine IV diluted to 10 ml with normal saline (NS) over 5 mins. Patients in group II received 2 µg/kg Fentanyl IV diluted to10 ml with NS over 5 mins. Patients were monitored for 5 minutes before induction and vital signs were recorded again. Pre-operative Ramsay’s sedation score was assessed. All patients were pre-oxygenated for 3 minutes with 100% oxygen. Intravenous injection propofol 2-2.5 mg/kg was used to induce all the patients. To enable laryngoscopy and intubation, succinylcholine (2 mg/kg) was administered intravenously. This was followed by intubation with suitable endotracheal tubes and maintenance on 50% oxygen, 50% nitrous oxide, and isoflurane/sevoflurane. Intubation was completed within 30 seconds of laryngoscopy in first attempt. To maintain intraoperative relaxation, a loading dosage of atracurium/vecuronium was administered, followed by a maintenance dose when breathing returned. All the parameters like HR, MAP, SBP, DBP and rate pressure product (RPP) were measured immediately after intubation followed by at 2, 3, 5, 7, and 10 minutes. The RPP was a measure of myocardial workload and oxygen consumption, calculated by heart rate × systolic blood pressure/100. To avoid trouble in recording data, the surgical interventions such as incision, nasogastric tube insertion and catheterization were allowed after 10 mins of induction. Reversal of neuromuscular blockade was carried out with intravenous injections of glycopyrrolate and neostigmine. Extubation was done when the patient was adequately recovered from the effect of neuromuscular blockade with a regular breathing pattern, good muscle tone/power, haemodynamically stable and was able to respond to verbal commands. Ramsay sedation score was used to assess post-operative sedation. In the post-operative period, patients were observed for side effects like hypotension, bradycardia, arrhythmia, bronchospasm, shivering and vomiting.

Statistical analysis

Open EPI software version 3.0 was used to calculate the sample size. The power was kept 80% with 95% confidence interval. Data obtained from the study was entered into Microsoft Excel datasheet. The results were stated as mean ± standard deviation. The statistical analysis was done using EPI software version 3.0. Chi-square test was used for demographic data and unpaired student t-test was used for inter-group comparisons. P value < 0.05 was considered significant and P value < 0.001 as highly significant.

The calculated sample size for the study was 58. The participants were randomly divided into two groups with equal number of participants (n = 29).

Demographic data

Mean age of participants in group I was 42.6 ± 10.4 years and in group II was 39.6 ± 7.1 years. Average weight of the participants in group I was 58.5 ± 8.66 kg and in group II was 59.2 ± 8.98 years. Regarding gender distribution, 51.7% (n=15) were females and 48.3% (n=14) were males in group I and 51.7% (n=15) were males and 48.3% (n=14) were females in group II.  Out of 29 patients in each group, majority (58.6%, n =17 in group I and 55.2%, n = 16 in group II) patients belonged to ASA grade II. The difference in the demographic parameters in both groups was not statistically significant.

Hemodynamic parameters

Pulse

Figure 1 below depicts changes in HR in both groups at various time intervals. Group I had a mean baseline heart rate of 88.40 ± 10.8 bpm, while group II had a mean of 90.5 ± 7.25 beats/min, with a statistically insignificant difference (P = 0.19). Dexmedetomidine and Fentanyl both reduced mean HR after induction, but reduction in HR was more in group I which was statistically significant (P = 0.001). There was a significant rise in HR in both groups, but more in group II (P = 0.005) post-intubation. Group I had a significantly lower HR at 2 min (P = 0.002), 3 min (P = 0.001), 5 min (P = 0.001), 7 min (P = 0.001) and 10 mins (P = 0.002) after intubation.

Figure 1. Comparison of pulse rate at different time intervals in two groups.

Systolic blood pressure

Figure 2 compares the SBP fluctuations in both groups over time. The mean SBP in group I at baseline was 120 ± 10.8 mmHg while patients in group II had a reading of 126 ± 7.1 mmHg. Patients in both groups had reduced SBP after completion of study drug (pre-induction), and the difference between the groups was highly significant statistically (P = 0.001). Dexmedetomidine group had significantly lower SBP at 2 mins, 3 mins, 5 mins, 7 mins and 10 minutes after intubation compared to those receiving fentanyl (P < 0.001).

Figure 2. Comparison of systolic blood pressure at different time intervals in two groups.

Diastolic Blood Pressure

As shown in figure 3, at baseline, patients receiving Dexmedetomidine had a mean DBP of 80.2 ± 3.6 mmHg and patients who got Fentanyl had a mean DBP of 84.6 ± 2.30 mmHg. The difference was statistically insignificant (P = 0.871). There was significant fall in DBP in both the groups after injection of study drug (78 ± 11.9 mmHg in group I vs 80.4 ± 5.2 mmHg in group II, P = 0.002). There was slight increase in DBP after intubation in group I and group II (80.2 ± 8.7 mmHg vs 86.9 ± 5.2 mmHg) respectively. Value reduced gradually and came below the induction value at 10 min in both the groups. Patients who received Dexmedetomidine showed significantly reduced DBP at all the time intervals compared to Fentanyl group across all time points (P < 0.05).

Figure 3. Comparison of diastolic blood pressure at different time intervals in two groups.

Mean Arterial Pressure

Figure 4 compares the MAP at various time intervals between two groups. The baseline MAP in group I was 82.3 ± 8.7 mmHg and in group II was 88.4 ± 5.2 mmHg (P = 0.265). After intubation, the mean MAP increased to 84.2 ± 7.9 mmHg in group I and to 94 ± 5.1 mmHg in group II (P = 0.002). Across all time intervals, group II consistently showed significantly higher MAP compared to group I (P < 0.05).

Figure 4. Comparison of mean arterial pressure at different time intervals in two groups.

Rate pressure product

Figure 5 presents the monitoring of the RPP for groups I and II across various time intervals. The RPP decreased over time in both the groups after intubation, but group II consistently exhibited significantly higher RPP values compared to group I across all time intervals (P < 0.05). 

Figure 5. Comparison of rate pressure product at different time intervals in two groups.

SpO₂

There was no statistically significant difference observed in SpO₂ levels of both the groups at all time intervals as shown in figure 6 (P > 0.05).

Figure 6. Comparison of SpO₂ at different time intervals in two groups.

Ramsay sedation score

Before induction (10 mins after injection of study drug) group I had statistically significant higher sedation score compared to group II (3.8 ± 1.1 vs 2.5 ± 0.8, P = 0.001). After extubation, patients in group I were more tranquil and co-operative compared to group II, which was also statistically significant (1.8 ± 0.2 vs 1.7 ± 0.4, P = 0.05).

Adverse events

Five patients from group I developed adverse effects, three patients had hypotension and two patients had bradycardia which resolved during recovery period without requiring any medication. In group II, six patients had adverse events, four patients developed vomiting, for which three of them required antiemetic and two patients developed shivering which was resolved uneventfully with non-pharmacological measures.

General anaesthesia routinely involves laryngoscopy and endotracheal intubation, which is associated with significant hemodynamic response due to stress. The response usually occurs as a result of sympathetic system stimulation. The magnitude of this response can be detrimental, particularly in patients with cardiovascular comorbidities, as it may lead to myocardial ischemia, arrhythmias, or stroke [3]. Various pharmacological agents, including opioids, β blockers and α agonists, are employed to mitigate this hemodynamic stress response. Dexmedetomidine and fentanyl are two such drugs belonging to α₂ agonist and opioid group, respectively. This study was conducted to compare the effectiveness of intravenous administration of either dexmedetomidine or fentanyl in attenuating the hemodynamic stress response associated with laryngoscopy and endotracheal intubation in patients undergoing surgery under general anaesthesia.

In this study, it was observed that both dexmedetomidine and fentanyl lowered HR from baseline with dexmedetomidine resulting in more stable haemodynamic and lower readings. This was similar to the findings observed in previous studies [7, 8]. Mahjoubifard et al. (2020) compared the hemodynamic response attenuation effects of dexmedetomidine, fentanyl and lidocaine. They reported that HR attenuation with dexmedetomidine in the third, fifth, and tenth minutes was substantially stronger than that with the other two medications. Dexmedetomidine's ability to reduce HR is attributed to its α₂ agonist activity, which decreases norepinephrine release.

Regarding the BP, it was observed that patients receiving dexmedetomidine had significantly lower SBP and DBP before induction as well as at all time intervals after intubation. This is similar to findings observed in other studies [9, 10]. It was observed in the previously published studies that patients receiving dexmedetomidine had lower SBP and DBP compared to those receiving fentanyl. The authors reported that dexmedetomidine maintained stable blood pressure after intubation, with only a slight decrease that was well-tolerated [9, 10]. In contrast, patients in the fentanyl group experienced a significant spike in blood pressure immediately after intubation, reflecting a less effective suppression of the sympathetic response. This shows that dexmedetomidine suppressed the sympathetic response more effectively, most likely due to its central sympatholytic properties. DBP increased less after intubation in the patients receiving dexmedetomidine as compared to fentanyl. This is consistent with the lower SBP found in the dexmedetomidine group, indicating that it can maintain more stable BP during sympathetic activation [11]. Although both dexmedetomidine and fentanyl provided stable haemodynamic, dexmedetomidine resulted in lower SBP throughout surgery.

It was found in this study that MAP was consistently significantly higher in patients receiving fentanyl as compared to dexmedetomidine. This higher MAP in Group II suggested a potential difference in response to anaesthetic interventions between the two groups. This is similar to findings obtained in other studies which shows significantly higher increase in MAP with fentanyl as compared to dexmedetomidine [12, 13]. MAP is a key indicator of tissue perfusion and is often monitored during anaesthesia to assess cardiovascular stability. Thus, dexmedetomidine offers a more reliable option for maintaining MAP within a safe range during laryngoscopy and intubation. Its ability to blunt the increase in MAP is particularly beneficial in patients prone to hypertensive episodes or at risk of end-organ damage due to significant fluctuations in blood pressure.

It was observed that RPP was significantly lower in the patients who received dexmedetomidine as compared to those who received the opioid fentanyl. This suggests that Group II experienced higher myocardial workload and oxygen demand compared to Group I. This is similar to the findings obtained in previously published studies [14, 15]. Patel et al. (2015) reported that with the infusion of either drug, the RPP reduced below the baseline, increased after intubation and returned to baseline 10 minutes post-intubation. They reported a significantly lower RPP in dexmedetomidine group, as compared to fentanyl group [15]. RPP, an indicator of myocardial oxygen demand, is a critical parameter in evaluating the cardiac stress response to intubation. Thus, the findings suggest that dexmedetomidine may be more protective in patients at risk of ischemic heart events during intubation.

In this study, the SpO₂ was maintained between 98-100% in both the groups with no significant difference. This was similar to the findings of study by Patel et al. (2015). In contrast to this, an older study reported fall in oxygen saturation to 94-95% after administration of dexmedetomidine which returned to normal after waking up the patient [16].

In this study, dexmedetomidine, known for its sedative properties, resulted in a significantly deeper level of sedation in comparison to fentanyl. Due to higher levels of sedation, patients in this group required fewer additional doses of anaesthetic. This was similar to the findings obtained in other studies [16, 17]. Sebastian et al. (2017) showed that dexmedetomidine produced more profound sedation, allowing for a smoother transition from induction to intubation. Patients receiving fentanyl required additional anaesthetics to maintain adequate sedation, while dexmedetomidine’s sedative effect was more sustained throughout the perioperative period.

In this study, hypotension and bradycardia were the side effects reported in patients receiving dexmedetomidine and vomiting and shivering were observed in patients receiving fentanyl. Similarly, in other studies, bradycardia and hypotension were observed more in patients receiving dexmedetomidine which responded to atropine and intravenous fluids, respectively [18].

Certain limitations of the study must be considered. Firstly, the sample size is low which makes it difficult to generalize the findings of the study. Secondly, the dose of fentanyl used is lower, which may be responsible for the insufficient effect of fentanyl in lowering the hemodynamic stress response.

Intravenous dexmedetomidine is more effective in reducing hemodynamic stress response to laryngoscopy and endotracheal intubation. It is of vital importance, particularly in high-risk patients undergoing surgery. Dexmedetomidine's ability to attenuate the hemodynamic stress response more effectively than fentanyl suggests its potential as a preferred agent during laryngoscopy and intubation. Moreover, its sedative effects provide additional benefits in reducing anaesthetic requirements, which may lead to a smoother induction and maintenance of anaesthesia. However, the use of dexmedetomidine is not without drawbacks. It is associated with a more pronounced bradycardic effect, which in some patients might necessitate careful monitoring or pharmacologic intervention. Further studies with larger sample sizes are required to confirm the effective dose and strengthen these findings.

Conflict of interest

The authors have no conflict of interest to declare

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