|Year : 2019 | Volume
| Issue : 2 | Page : 67-73
Hemodynamic changes with intravenous dexmedetomidine and intravenous esmolol for attenuation of sympathomimetic response to laryngoscopy and tracheal intubation in neurosurgical patients: A comparative study
Bitan Sen, Ashok Chaudhary, Jayashree Sen
Department of Anaesthesia, JNMC and AVBRH, Wardha, Maharashtra, India
|Date of Submission||01-Apr-2019|
|Date of Decision||08-May-2019|
|Date of Acceptance||13-May-2019|
|Date of Web Publication||25-Nov-2019|
Dr. Jayashree Sen
Department of Anaesthesia, JNMC and AVBRH, Sawangi, Wardha, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Dexmedetomidine a highly selective α2-adrenoreceptor agonist and esmolol an ultra-short-acting β1-cardioselective adrenergic receptor blocker appear to be quite suitable to control the detrimental effects of laryngeal and tracheal stimulation. The study was conducted to compare the efficacy and safety of dexmedetomidine and esmolol for attenuation of hemodynamic responses to laryngoscopy and intubation in patients of elective neurosurgical procedures under general anesthesia. Materials and Methods: Sixty patients of age 20–60 years, the American Society of Anesthesiologists I and II posted for neurosurgical procedures, randomized into two groups of 30 each to receive dexmedetomidine (Group D): 1 μg/kg and esmolol (Group E): 1.5 mg/kg, both diluted to a total volume of 20 mL with 0.9% saline, infused intravenous over a period of 10 min, before 3 min of induction. Changes in heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), rate pressure product (RPP), any side effects associated with the drugs during the study, i.e., 20 min of intubation, were observed and statistically analyzed. Result: There was no statistically significant difference (P = 0.195) in mean HR between Groups D and E during intubation but from the 1st min after intubation (T1) (0.0001) till 20th min (T20) (0.0041) a statistically significant difference in mean HR, mean SBP (P = 0.0001), mean DBP (P < 0.05), mean arterial pressure (P < 0.05), and mean RPP (P = 0.0001) was observed. Conclusion: Infusion of dexmedetomidine was better as compared to esmolol hydrochloride in attenuation of hemodynamic response to laryngoscopy and tracheal intubation.
Keywords: Dexmedetomidine, esmolol, neurosurgical patients, tracheal intubation
|How to cite this article:|
Sen B, Chaudhary A, Sen J. Hemodynamic changes with intravenous dexmedetomidine and intravenous esmolol for attenuation of sympathomimetic response to laryngoscopy and tracheal intubation in neurosurgical patients: A comparative study. J Datta Meghe Inst Med Sci Univ 2019;14:67-73
|How to cite this URL:|
Sen B, Chaudhary A, Sen J. Hemodynamic changes with intravenous dexmedetomidine and intravenous esmolol for attenuation of sympathomimetic response to laryngoscopy and tracheal intubation in neurosurgical patients: A comparative study. J Datta Meghe Inst Med Sci Univ [serial online] 2019 [cited 2020 Apr 4];14:67-73. Available from: http://www.journaldmims.com/text.asp?2019/14/2/67/271555
| Introduction|| |
In 1921 Rawbotham and Magill, Reid and Brace  in 1940, and King et al. in 1951 described the responses on circulation due to laryngeal and tracheal stimulation. The rise in heart rate (HR) and blood pressure (BP) and the disturbances caused thereby in the cardiac rhythm are short lived, they may have undesirable detrimental effects in patients, especially with diseases of cardiovascular or neurosurgical system or anomalies of cerebral vessel, undergoing surgery under anesthesia., To preserve the cerebral homeostasis control and prevention of untoward effects on hemodynamic responses, many strategies have been advocated at different levels of the reflex arc. To block the efferent pathway and the effector sites with drugs can be the mainstay of our study.
- Dexmedetomidine, an imidazole derivative, a highly selective α2-adrenoreceptor agonist, decreases systemic adrenaline, and noradrenaline production and has negative chronotropic and inotropic effect
- Esmolol, an ultra-short-acting β1-cardioselective adrenergic receptor blocker, appears to be quite suitable for use during a short-lived stress such as tracheal intubation.
Aim and objectives
This study aims to study and compare the efficacy and safety of dexmedetomidine and esmolol for attenuation of hemodynamic responses to laryngoscopy and intubation in patients of elective neurosurgical procedures under general anesthesia.
To observe the:
- Changes in HR
- Changes in systolic BP (SBP), diastolic BP (DBP) pressure
- Changes in myocardial oxygen demand using the rate pressure product (RPP)
- The side effects associated with the drugs used during the study.
| Materials and Methods|| |
The study had been conducted in a rural hospital medical college, during August 2016–September 2018, having got approval from the institutional Ethics Committee and written informed consent from the patients in their vernacular language.
This is a prospective randomized, interventional study.
A total of 60 patients aged 20–60 years, the American Society of Anesthesiologists (ASA) physical status I or II, either gender, scheduled for elective neurosurgical procedures were included in this study. Groups allocation was done randomly into 2 of 30 patients each, with the help of a computer-generated table of random numbers.
- Group D (dexmedetomidine) – 1 μg/kg body weight diluted to a total volume of 20 mL with 0.9% saline intravenous (IV) over a period of 10 min
- Group E (esmolol) – 1.5 mg/kg body weight diluted to a total volume of 20 mL with 0.9% saline IV over a period of 10 min.
All the drugs had been prepared by an independent anesthesiologist not involved in the study, in identical syringes to be infused with infusion pump, 3 min before induction of anesthesia.
Patient selection, inclusion and exclusion criteria
In this study, the patients were selected from the Indian rural population with the following criteria:
- Patient scheduled for elective neurological surgeries for tracheal intubation using Macintosh laryngoscope
- Age between 20 and 60 years of either gender
- Weight between 40 and 70 kg
- Patient with ASA Grades I and II
- Mallampati airway assessment of Grades I and II.
- Unwilling patient
- Emergency surgeries
- Patient with ASA Grade III or higher
- Patient with a history of known allergies to study drugs
- Anticipated difficult intubation according to LEMON criteria/more than one attempt of intubation/nasal intubation/retrograde intubation
- Patient with cardiovascular diseases and severe respiratory diseases/moderate to severely raised intracranial pressure (ICP) (from clinical signs and symptoms)
- Pregnant patient and breastfeeding mothers
- Patient on beta blockers or calcium channel blockers or sympatholytic drugs or pregabalin
- Systemic illness such as hypertension, diabetes, hepatic failure, renal failure, hyperthyroidism, or endocrine disorders.
Preanesthetic evaluation of all patients, done a day before the surgery, consisted of:
- Detailed history
- Physical examination
- Systemic examination
- Routine investigations
- Special investigations wherever required.
Patients were informed about the nature of the study, and after proper preanesthetic counseling, a written and informed consent had been obtained.
All patients had been kept nil by mouth for 6 h before surgery. Tablet alprazolam 0.5 mg was given the night before the surgery to allay anxiety.
On the day of surgery, patients were shifted to the operation theatre 15 min before induction. IV line secured with 18 G IV cannula, pulse oximeter, noninvasive BP (NIBP), electrocardiogram (ECG) monitor, and end-tidal carbon dioxide (EtCO2) had been attached. HR, BP both SBP, DBP, RPP recorded had been considered as baseline (BL) value. Injection glycopyrrolate 0.004 mg/kg as an antisialogogue, ondansetron 0.08 mg/kg as anti-emetic, had been given intravenously and infusion of normal saline started at the rate of 2 ml/kg/h.
Immediately after the administration of either dexmedetomidine or esmolol, preoxygenation done with 100% oxygen by mask for 3 min, premedication given, consequently, all the patients were induced with injection propofol 2 mg/kg till the loss of eyelash reflex. Neuromuscular blockade had been achieved by injection atracurium besylate 0.5 mg/kg. Intermittent-positive pressure ventilation continued with 100% O2 and after adequate relaxation (3–4 min), laryngoscopy had been done using standard Macintosh blade. Intubation time used to be limited to ≤30 s by a consultant with appropriate sized, disposable, high volume low pressure, portex cuffed endotracheal tube in all the cases in one intubation attempt which is defined as an act of introducing laryngoscope blade between the incisors into the oropharynx to achieve endotracheal view.
None of the patients in any group required any external laryngeal manipulation to improve glottic visualization which might have caused a more laryngoscopic response. Treatment for significant hypotension would be with 6 mg IV boluses of ephedrine, significant bradycardia with 0.6 mg atropine IV. Patients in whom significant hypotension or bradycardia would occur during the study be treated and dropped from the study.
All the patients were ventilated with closed circuit and anesthesia was maintained with oxygen 40% and air 60%, sevoflurane 1%–1.5%, and intermittent boluses of injection atracurium. Ventilation used to be adjusted to maintain an ETCO2 value between 30 and 35 mmHg with the probability of increased ICP secondary to their pathology. Injection mannitol would be administered wherever required in dose of 1–1.5 g/kg and injection fentanyl l 2 μg/kg after 20 min of intubation, i.e., at the end of our study.
Preoperative vitals were monitored using ECG, pulse oximeter, NIBP, and capnography. BL parameters such as HR, SBP, DBP, ETCO2 SPO2, and RPP were recorded before the administration of study drugs (BL), immediately after study drug given (intra-abdominal sepsis [IAS]), during intubation (DI) and at 1 (T1), 3 (T3), 5 (T5), 7 (T7), 10 (T10), 15 (T15), and 20 (T20) min after intubation. No surgical intervention was allowed throughout the study.
After the completion of surgery, neuromuscular blockade had been reversed with injection neostigmine 0.05 mg/kg IV and injection glycopyrrolate 0.004 mg/kg IV and patients were extubated on efforts of spontaneous respiration and were shifted to the recovery room.
Observations related to side effects of drugs such as tachycardia (HR >100 beats/min), bradycardia (HR <60 beats/min), hypotension (BP <90/60 mmHg), arrhythmia, or any allergy to the study drugs and anesthesia-related problems were made and attended appropriately.
Endpoint of the study
Our study continued till 20th min after intubation.
Statistical analysis was done using Chi-square test, Student's paired t-test, one-way ANOVA and software used in the analysis were SPSS 22.0 version (IBM, USA) and GraphPad Prism 6.0 version (GraphPad Software, San Diego, California) and P < 0.05 is considered as the level of statistical significance.
| Results|| |
All the 60 patients recruited were included in the study. The demographic profile was comparable between the groups.
The mean heart values [Figure 1] in the groups were comparable, and the BL values were found to be insignificant (P > 0.05).
|Figure 1: Comparison of changes in mean heart rate values at different time intervals|
Click here to view
After the administration of study drugs, there was a statistically significant difference across the groups (P = 0.0001) in the mean HR. DI there was no statistically significant difference between Groups D and E (P = 0.195). Dexmedetomidine attenuated mean HR by 12.1%, which was maximum attenuation of mean HR among the groups.
Esmolol attenuated the HR by 11.24% from BL.
During the 1st min after intubation (T1) till 20th min (T20), there was a statistically significant difference (P < 0.05) in mean HR across the groups indicating a constant reliable attenuation of mean HR in dexmedetomidine group [Figure 1].
The mean SBP values [Figure 2] were comparable, and the BL values were found to be insignificant in all the groups (P > 0.05).
Immediately after the administration of study drugs (IAS), when the mean SBP was compared among the groups, there was a statistically nonsignificant difference across the Groups D and Group E (P = 0.151). This indicated that the mean SBP was reduced IAS in Groups D and E. DI, there was a statistically significant difference between Groups D and E (P = 0.0001), indicating that there was a rise in mean SBP in Group E during laryngoscopy.
In dexmedetomidine group, P value was statistically significant (P > 0.05) throughout the study when compared with BL, indicating prolonged duration of action on mean SBP.
In esmolol group significant P value (P < 0.05) was seen in IAS, DI, T1 and nonsignificant at T3, T5, T7, T10, T15, T20 (P > 0.05) indicating its short duration of action [Figure 2].
The mean DBP values [Figure 3] in all the groups were comparable, and the BL values were found to be insignificant in all the groups (P > 0.05).
DI there was a statistically significant difference between Groups D and E (P = 0.0001), indicating that there was rise in mean DBP in Group E during laryngoscopy.
In dexmedetomidine group, P value was statistically significant (P < 0.05) throughout the study when compared with BL, indicating the prolonged duration of action on mean DBP. In esmolol group, significant P value (P < 0.05) was seen in IAS, DI, T1 and nonsignificant at T3, T5, T7, T10, T15, T20 (P > 0.05) indicating its short duration of action [Figure 3].
As shown in [Figure 4], DI, there was a statistically significant difference between Groups D and E (P = 0.0001), indicating that there was a change (rise) in mean RPP in Group E during laryngoscopy and intubation. During the 1st min after intubation (T1) till 20th min (T20), there was a statistically significant difference (P < 0.05) in mean RPP across the groups. In Group E, mean RPP was significantly below its BL value after the administration of study drug, after intubation, it was above the BL, and thereafter, it was consistently toward its baseline value till T20. This indicates dexmedetomidine was more effective in reducing the mean RPP as compared to esmolol [Figure 4].
| Discussion|| |
In 1940, Reid and Brace  were the first to recognize the hemodynamic responses such as hypertension, tachycardia, atrial and ventricular extrasystoles, delayed conduction time following laryngoscopy and endotracheal intubation. Their postulation was that the disturbances in the cardiovascular system were reflexive in nature caused by the stimulation of epipharynx and laryngopharynx and mediated by the vagus nerve.
Hassan et al. reported a high incidence of increase in HR, SBP, and plasma catecholamine level after laryngoscopy and intubation. Devault et al. in 1960, observed that tachycardia, a pressor response, consistently accompanied tracheal intubation done under light general anesthesia. The duration of laryngoscopy also has been found to be one of the important factors influencing the cardiovascular responses. Bachofen et al. in their study for preventing sympathetic response, observed that there happens a linear increase in HR and BP mainly systolic, during first 45 s of laryngoscopy. In our study, we have limited laryngoscopy and intubation timing to ≤30 s. Sulaiman et al. found that the elevation in arterial pressure typically starts within 5 s of laryngoscopy, peaks in 1–2 min and returns to control levels within 5–10 min. Forbes and Dally  reported that immediately after laryngoscopy and endotracheal intubation, there had been an average increase in mean arterial pressure of 25 mm of Hg. Intubation-induced hypertension may be associated with an acceleration in ICP, intracranial bleeding, and adverse hemodynamic effects which may increase the morbidity and prolonged hospital stay in neurosurgical patients.
The criteria for selection of appropriate drug to prevent sympathetic response was stated by Bachofen et al.
Dexmedetomidine, a selective α2 agonist with an onset of action at about 5 min at a dosage of 1 μg/kg, has a peak effect which occurs within 15 min. Its elimination half-life is about 2–3 h. It provides neurovegetative protection and has predictable cardiovascular and respiratory effects in a dose-dependent manner. Higher doses of dexmedetomidine have been associated with a significant increase in the incidence of bradycardia and hypotension. Rapid administration of dexmedetomidine might produce tachycardia, bradycardia, and hypertension followed by hypotension.
In our study, we chose to administer injection dexmedetomidine IV infusion over a period of 10 min in the dose of 1 μg/kg diluted to a total volume of 20 mL with 0.9% saline. Recent studies have shown that dexmedetomidine decreases brain blood flow and cerebrospinal fluid (CSF) pressure without cerebral ischemia  and administration of dexmedetomidine to achieve serum levels of 0.6 mg/mL and 1.2 mg/mL produced the reduction of CSF pressure and concomitant reduction of the cerebral metabolic rate of oxygen.,
Beta-adrenergic blockers, another group of pharmacological agents was used for blunting the hemodynamic responses to laryngoscopy and intubation.,, Esmolol, a selective beta-blocker was introduced in1986, fascinated many investigators because of its short duration of action and no risk of developing perioperative bradycardia or hypotension.
Miller et al. in 1991 used different doses of injection esmolol 1.5 mg/kg and 3 mg/kg. They observed adverse effects like hypotension with higher doses of esmolol during induction and claimed optimal results with lesser dose. Sharma et al. in their study concluded that injection esmolol 1–1.5 mg/kg is the most effective in attenuating hemodynamic responses during laryngoscopy and intubation without major adverse effects.
This was the basis for using a smaller dose of injection esmolol (1.5 mg/kg) as our study drug, which was given as IV infusion over a period of 10 min in the dose of 1.5 mg/kg diluted to a total volume of 20 mL with 0.9% saline. None of our patients developed any side effect such as severe hypotension (fall in BP >25% as compared to BL).
Singh et al. in their study concluded that injection esmolol 1.5 mg/kg single IV bolus given 3 min before induction was very effective when compared to 90 s and 6 min earlier in our study, we administered both the study drugs in infusion for 10 min followed by laryngoscopy and intubation 3 min later. Therefore, injection dexmedetomidine (1 μg/kg) body weight, diluted to 20 mL IV infusion and esmolol (1.5 mg/kg) body weight, diluted to 20 mL IV infusion appear best to fulfill the above criteria.
Liu et al. used esmolol infusion to control hemodynamic responses associated with intubation, found a significant decrease in HR and SBP prior to induction and postintubation, the increase was 50% less in the esmolol-treated patients compared to the placebo group. In our study [Figure 1], immediately after giving the study drug esmolol, there was a fall in mean HR by 14.61%, during laryngoscopy and DI the fall was by 11.24% from their BL values.
Keniya et al. stated that the pretreatment with dexmedetomidine 1.0 μg/kg attenuated, but not totally obtunded the cardiovascular response to tracheal intubation after induction of anesthesia. We found in our study [Figure 1] that the BL values of the mean heart were insignificant in the groups (P > 0.05). After the administration of study drug, the mean HR became statistically significant across the groups (P = 0.0001). In dexmedetomidine group, there was a fall in mean HR by 12.1% during laryngoscopy and intubation, at T1 by 14.07%.
From T3 (70.8 ± 9.24) to T20 (68.4 ± 8.11), the mean HR remained low throughout in dexmedetomidine group. A statistically significant difference in mean HR across the groups was observed till 10th min (T10).
The BL values of the mean SBP [Figure 2] were found to be insignificant in all the groups (P > 0.05).
Saif GM et al. found in their patient of Group I who received an infusion of Esmolol, and the patients of Group II (control) received an infusion of 5% dextrose as placebo. They found SBP at 3 mins and 5 mins after intubation no statistically significant variation from the base line (P > 0.01) in the study group, there was but significant change statistically (P < 0.01) in the control group where the SBP increased at 3 mins and at 5 mins after intubation from the base line value.
In our study [Figure 2], in esmolol group, the increase in mean SBP was 8.36% during laryngoscopy, at T1 6.76%, from the BL value. Hence, there was no attenuation of mean SBP response in Group E during laryngoscopy. At T3, the mean SBP reached the BL value (120.43 ± 12.07) and remained around the BL till the end of the study. 1st min after intubation (T1) till 10th min (T10), there was a statistically significant difference in mean SBP across all the groups.
At 15th min (T15) and 20th min (T20), there was no statistically significant difference in mean SBP in esmolol group (P = 0.881).
Kaushal et al. found in their study that DI, there was a reduction in SBP by 16.45% in Group A where injection dexmedetomidine was given as a bolus dose of 1 μg/kg over 20 min before induction of anesthesia, and an increase by 10.49% in SBP from BL values in Group B where similar volumes of isotonic saline in the same manner was given. In our study [Figure 2] also DI, the dexmedetomidine group produced a significant reduction in mean SBP value (11.40%).
The BL values of mean DBP [Figure 2] was statistically insignificant (P > 0.05) in the groups. Srivastava et al. found in their study of control group (Group C), group dexmedetomidine (Group D), and group esmolol (Group E), DBP values were statistically significantly lower in the Group D after induction and all time observation of intubation, when compared with the Groups C and E (P < 0.001). In Group C, there was a statistically significant change after intubation at 1–10 min period. In Group D, there was no statistically significant increase after intubation at any time intervals, while in Group E, there was a statistically significant increase after intubation at 1, 2, and 3 min. Changes in the DBP observed in the three groups during the study. P < 0.05 within group (vs. BL value), P < 0.001 compared with Group C, P < 0.001 Group D versus Group E.
We also had similar observations [Figure 3] that during laryngoscopy and intubation, there was a fall in mean DBP by 11.19% in dexmedetomidine group and esmolol group a rise by 15.18% from their BL values and there was a statistically significant difference between Groups D and E (P = 0.0001). At 1st min after intubation (T1), there was a fall in mean DBP in the dexmedetomidine group by 13.01%, but in esmolol group, a rise by 8.07% above its BL value. During the 1st min after intubation (T1) till 10th min (T10), there was a statistically significant difference in mean DBP across all the groups.
Rise in RPP (HR [PR] × SBP) increases the risk of myocardial ischemia  leading to myocardial infarction, acute cardiac failure, pulmonary edema, and arrhythmias. Gobel et al.,,,,,,, studied normotensive cases with ischemic heart disease during exercise. They found that HR multiplied by SBP is a good hemodynamic predictor of myocardial oxygen consumption.
Singh et al. found that percentage change in RPP = -1.86% versus 17.25% in esmolol group versus control group respectively at 5 min.
In our study [Figure 4], the fall in the RPP in esmolol group was for a short period (from IAS to T3). After 3 min of intubation (T3), the mean RPP reached the BL and remained around the BL value throughout the study, i.e., till T20.
Sharma et al. found no significant difference in mean RPP among the groups at BL (P > 0.05). RPP increased from BL 1 min after intubation in all the groups. The values in Group D (dexmedetomidine) were significantly lower compared to Group C (control) and Group E (esmolol) and this trend was observed up to 10 min after intubation. Similarly, RPP values in Group E (esmolol) were significantly lower than that of Group C (control) up to 7 min after intubation.
In our study [Figure 4], the BL mean RPP was in statistical comparison. During laryngoscopy and intubation, there was a fall in mean RPP by 21.71% in dexmedetomidine group and esmolol group by 4.31%, at T1 the fall in mean RPP in dexmedetomidine group was by 23.6%, in esmolol group by 5.27% from its BL value.
From T3 to T20, the mean RPP remained below the BL value throughout in dexmedetomidine group, in esmolol group, the mean RPP reached near BL value at T3 [Figure 4]. Thus, the patients in dexmedetomidine group were having more cardioprotection than esmolol groups as mean RPP is an indirect indicator of myocardial oxygen demand, especially in neurosurgical patients.
| Conclusion|| |
We conclude that in neurosurgical patients, dexmedetomidine infusion is better than infusion of esmolol hydrochloride in suppressing the sympathoadrenal reflex activity for attenuation of hemodynamic response to laryngoscopy and endotracheal intubation.
The doses of injection dexmedetomidine and injection esmolol hydrochloride used in our study did not show any adverse effect such as bradycardia, hypotension, and allergic reaction in any of the groups because large doses were not used in our study.
The serum levels of stress markers such as cortisol and catecholamine level during laryngoscopy and intubation were not measured; hence, the differences in neuroendocrine responses to laryngoscopy and intubation between the study drugs could not be compared.
Financial support and sponsorship
Indian Council of Medical Research.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]