|Year : 2022 | Volume
| Issue : 5 | Page : 314-320
A comparative study of intravenous low doses of dexmedetomidine, fentanyl, and magnesium sulfate for attenuation of hemodynamic response to endotracheal intubation
Sharmishtha Shukla1, Reena R Kadni2, Joel J Chakravarthy2, K Varghese Zachariah2
1 Department of Anaesthesia, University Hospitals of Derby and Burton NHS Trust, Derby, United Kingdom
2 Department of Anaesthesia, Bangalore Baptist Hospital, Bengaluru, Karnataka, India
|Date of Submission||19-Sep-2020|
|Date of Decision||20-Oct-2022|
|Date of Acceptance||09-Nov-2022|
|Date of Web Publication||13-Dec-2022|
Reena R Kadni
Department of Anaesthesia, Bangalore Baptist Hospital, Bengaluru, Karnataka
Source of Support: None, Conflict of Interest: None
BACKGROUND: Endotracheal intubation is an integral part of general anesthesia. The hemodynamic stress responses associated with it, though transient, are unpredictable and variable. In comparison with healthy individuals, those with comorbid health issues can have life-threatening complications with this sympathetic response. Hence, in this study, we compared the efficacy of intravenous low doses of dexmedetomidine, fentanyl, and magnesium sulfate (MgSO4) in reduction of the hemodynamic response to endotracheal intubation.
MATERIALS AND METHODS: This prospective randomized study compared three groups of dexmedetomidine (0.6 μg/kg) (Group D), fentanyl (2 μg/kg) (Group F), and MgSO4 30 mg/kg (Group M). A total of 105 American Society of Anesthesiologist's 1 and 2 patients were selected with 35 in each group. The hemodynamic variables recorded at baseline, during induction and intubation up to ten minutes were pulse rate, systolic blood pressure, diastolic blood pressure, and mean blood pressure. The assessment of quantitative and qualitative data was done with the one-way ANOVAs, Student's t-test, and Chi-square test. Analysis of variance was done by post hoc tests.
RESULTS: There were statistically significant differences that were observed with dexmedetomidine and fentanyl groups in respect to heart rate and blood pressure responses to laryngoscopy and intubation when compared to MgSO4. A significant attenuation of response from baseline values was also noted with dexmedetomidine and fentanyl groups.
CONCLUSION: Efficacy of low doses of both dexmedetomidine and fentanyl was equipotent in attenuating response in comparison with MgSO4, and we conclude that dexmedetomidine can serve as an alternative to fentanyl.
Keywords: Dexmedetomidine, fentanyl, intubation response, low dose, magnesium sulfate
|How to cite this article:|
Shukla S, Kadni RR, Chakravarthy JJ, Zachariah K V. A comparative study of intravenous low doses of dexmedetomidine, fentanyl, and magnesium sulfate for attenuation of hemodynamic response to endotracheal intubation. Indian J Pharmacol 2022;54:314-20
|How to cite this URL:|
Shukla S, Kadni RR, Chakravarthy JJ, Zachariah K V. A comparative study of intravenous low doses of dexmedetomidine, fentanyl, and magnesium sulfate for attenuation of hemodynamic response to endotracheal intubation. Indian J Pharmacol [serial online] 2022 [cited 2023 Jan 29];54:314-20. Available from: https://www.ijp-online.com/text.asp?2022/54/5/314/363402
| » Introduction|| |
Endotracheal intubation is an important procedure practiced in the field of anesthesia. It is associated with airway manipualation which stimulates the pharyngeolaryngeal and tracheolaryngeal nociceptors leading to hemodynamic stress response which can be deleterious to patients with limited cardiac reserve and with other comorbid conditions such as valvular heart disease, abnormal cardiac rhythms, heart blocks, difficult airway, uncontrolled hypertension, raised intracranial pressure, pulmonary hypertension, asthamatics, or chronic obstructive lung diseases. Extreme hemodynamic variations with marked sympathetic activity such as tachycardia and hypertension are observed with airway handling procedures., Due to imbalanace in oxygen demand and supply to the heart, this stress response can be detrimental to an extent leading to myocardial infarction, pulmonary edema, arrythmias, cerebrovascular accidents such as hemorrhage, and other complications in susceptible patients. Dexmedetomidine, fentanyl, and magnesium sulfate (MgSO4) are studied and known to decrease the hmodynamic response during intubation in various doses. The following study compared the effects of low doses of intravenous (IV) dexmedetomidine, fentanyl, and MgSO4 on hemodynamic variables during endotracheal intubation under general anesthesia (GA). All three are potent analgesics, decrease catecholamine levels and are commonly used drugs in anesthesia practice. Lower dosages of each drug were chosen to help in providing opiod-free balanced anesthesia, assist enhanced recovery from anesthesia, and reduced the incidence of side effects associated with these drugs such as bradycardia, sedation, and delayed recovery from anesthesia.
We hypothesized that low dose of dexmedetomidine (0.6 μg/kg) can be more effective than low doses of fentanyl (2 μg/kg) and MgSO4 (30 mg/kg) in reducing the hemodynamic stress response during laryngoscopy and intubation.
| » Materials and Methods|| |
This study is a prospective, double-blinded and randomized clinical trial and was carried out after getting approval from the Institutional Ethics committee reference number ANA/67/2014 dated December 23, 2014, and was conducted from January 2015 to December 2015. It adheres to the applicable CONSORT guidelines [Figure 1].
Patients aged between 18 and 55 years, belonging to American Society of Anesthesiologist's (ASA) grade 1and 2 for elective surgeries under GA with controlled mechanical ventilation were selected. These patients were included after obtaining informed written consent. Patients with uncontrolled hypertension, ischemic heart disease, arrhythmias, on beta-blockers, heart blocks, atrioventricular dysfunction, anticipated difficult intubation/multiple attempts more than 2 or time duration of laryngoscopy more than 20 s of intubation were excluded from the study.
The sample size was 105, patients were randomly allocated to three different groups (D, F and M) with 35 in each using block allocation and concealment method as described. The number in each block was calculated using the formula 2n (where n is the number of drugs). We got a block size of 6. With the sample size of 105, we got a total of 18 blocks. All possible allocation sequence was assigned numbers from 1 to 20. The computer-generated random numbers were taken. The first digit of each number was taken to give the corresponding allocation sequence to each block. If the first number was 0, then the second number would be taken for the same.
This allocation sequence was revealed by an anesthesiologist not paticipating in the study. The primary investigator was kept unaware of the allocation sequences. Random numbers were concealed using the opaque envelopes and were opened just before the administration of block. The drugs were loaded and given according to the sequence.
The study instrument was the patient pro forma which included patient's name, age, gender, weight, ASA 1 or 2, patient's particulars, indication for surgery, and hemodynamic parameters were recorded at baseline (T0) and 5 (T1) and 10 (T2) min after test drug and 1 (T4), 3 (T5), 5 (T6), and 10 (T7) min after intubation.
Fasting guidelines were adhered to and premedication with oral ranitidine 150 mg and diazepam 10 mg was done. On arrival at the operation theater, patient's baseline hemodynamic parameters were recorded (basal reading T0) and IV cannula was secured.
According to the randomization, the patients received IV dexmedetomidine 0.6 μg/kg or IV fentanyl 2 μg/kg or IV MgSO4 30 mg/kg in 10 ml normal saline through a syringe pump over a period of 10 min at the rate of 60 ml/h before induction. After 5 min of stabilization (T1) and at 10 min of giving the test drug (T2) systolic blood pressure, diastolic blood pressure, and mean blood pressure (SBP, DBP, and MAP), heart rate (HR), and oxygen saturation (SPO2) were recorded. Patients were monitored with ASA standard monitors (Philips).
After preoxygenation, IV Propofol 2 mg/kg was used as an induction agent and neuromuscular block was achieved with IV Atracurium 0.5 mg/kg. Oxygenation and depth of anesthesia were maintained by mask ventilation with 50% O2, 50% air and isoflurane to maintain a minimum alveolar concentration of one through anesthesia work station (Datex Ohmeda). BP, HR, and SPO2 were recorded at 2 min (T3) after induction. Intubation done with endotracheal tube (Smiths Portex) was done by a consultant more than 3 years' experience and confirmation of its position were done by auscultation and capnography at 3 min after induction. The patient was put on the volume control mode on a ventilator to maintain EtCO2 of 30–35 mmHg. At 1 min (T4), 3 min (T5), 5 min (T6), and 10 min (T7) after laryngoscopy and intubation, hemodynamic parameters were recorded. Any fall in SBP to < 20% was planned to be treated with IV ephedrine 3 to 6 mg and bradycardia with HR <60 beats/min with IV atropine 0.6 mg. No form of the stimulus was applied during this period. Analgesics such as morphine, paracetamol, and fentanyl were given to all three groups after 10 min. The surgery commenced after 10 min of intubation as per the GA protocol. Patients were extubated at the end of the surgery.
The comparison of quantitative data and descriptive statistical methods (mean, standard deviation) was done with one-way ANOVA and Student's t-test. Qualitative data were assessed by the Chi-square test. The comparisons were considered statistically significant with (P < 0.05) and extremely significant with (P < 0.001) in a confidence interval of 95%. Statistical analysis was done with SPSS (Statistical Package for the Social Sciences) SPSS Inc. IBM, Chicago, United States, for Windows version 16.0. Post hoc tests used in analysis of variance were Tukey's Honestly significant difference (HSD) and Scheffe's test.
The sample size was calculated based on the mean HR after 5 min between two groups (dexmedetomidine and MgSO4). The difference in HR was maximum in these two groups; hence, these two groups were used to get a higher sample size. At a power of 90% and a confidence interval of 99%, the sample size was calculated as 35 per group. The total sample size was 105. On compensating for loss to follow-up, an additional 15% of the sample size was added.
| » Results|| |
The three groups had no significant differences with subject to the demographic profile of the patients (P > 0.05) and were comparable concerning age, gender, weight, and ASA physical status.
The comparison of the three groups in respect to HR showed statistically significant increases after giving test drugs, (T1, T2), after induction agent (T3) and after intubation (T5 and T6) [Table 1]. The baseline values were comparable without any significant differences. The increase in HR in the MgSO4 group was more significant than the other two groups after giving test drug, at induction and 3–5 min after intubation but settled by 10 min.
There were more statistically significant differences on post hoc tests intergroup comparison of HR between fentanyl and MgSO4 groups on effects on HR after intubation with P < 0.05, whereas between dexmedetomidine and MgSO4, significant differences were not observed after intubation [Table 2]. Dexmedetomidine and fentanyl were comparable before and after intubation in their responses.
|Table 2: Intergroup comparison of P values of heart rate among three groups dexmedetomidine, fentanyl, and magnesium sulfate in based on post hoc test results|
Click here to view
On comparing the three drugs for their effects on SBP, significant differences (with P < 0.05) were found after giving induction agent (T3) and at all times after intubation (T4, 5, 6, 7) [Table 3]. There was a drop in SBP in all groups after induction of anesthesia and significant rise was observed in M group at 1 min after intubation. Post hoc intergroup comparison of SBP showed statistically significant differences between fentanyl and MgSO4 from time of induction agent given till 10 min after intubation [Table 4]. Between dexmedetomidine and MgSO4 groups, there were significant differences at 3 min after intubation till 10 min. Fentanyl and dexmedetomidine were comparable and were better in controlling the SBP response after intubation than MgSO4.
|Table 3: Comparison of systolic blood pressure (mmHg) in three groups of patients|
Click here to view
|Table 4: Intergroup comparison of systolic blood pressure (mmHg) among three groups dexmedetomidine, fentanyl, and magnesium sulfate based on post hoc test results|
Click here to view
On comparing the three drugs with relation to DBP and MAP, there was a statistically significant decrease seen with P = 0.018 at 5 min after intubation (T6). Intergroup comparison showed a significant difference between fentanyl and MgSO4 at T6 for DBP. With MAP, there was a significant difference between fentanyl and MgSO4 and dexmedetomidine and MgSO4 at T6. Dexmedetomidine and fentanyl groups did not show any significant differences concerning DBP and MAP.
There was a statistically significant increase in HR with all three drugs when compared to their baseline values and to the mean values over 10 min after intubation and more significantly with MgSO4. Extremely significant reduction of SBP and MAP was seen with dexmedetomidine and fentanyl groups when compared to their baseline values. DBP was extremely reduced with fentanyl than with dexmedetomidine.[Table 5].
|Table 5: Comparison of baseline values (T0) with mean value over 10 min after intubation in each group for all parameters|
Click here to view
| » Discussion|| |
The aim of endotracheal intubation is to secure a definitive airway. Unfortunately, it leads to a undesirable cascade of pathophysiological responses. This may cause adverse outcomes in the selected patient population who possess comorbid health issues. Various medications are in use to reduce this hemodynamic response, but not all are beneficial in aspects of analgesia and amnesia which can further assist the anaesthesia service to the patient. Furthermore, the upcoming role of opiod-free anesthesia led us to this trial to compare nonopioid drugs like dexmedetomidine and MgSO4 with fentanyl.
The receptor selectivity of dexmedetomidine is dose-dependent, more of α-2 selectivity is observed with slow infusions, and both α-1 and α-2 activities resulted from high doses or rapid infusions. The baroreceptor reflex response is known to be well preserved in patients who received dexmedetomidine. Higher doses are associated with bradycardia, hypotension, and sedation.
The vasodilatory and antidysrhythmic effects of MgSO4 have been presumed to protect against hypertensive responses to direct laryngoscopy and tracheal intubation. It performs as a cardioprotective drug by reducing the increase in intracellular calcium ion flux that accompanies myocardial ischemia followed by reperfusion., MgSO4 toxicity is associated with prolonged neuromuscular block and sedation.
Fentanyl is regularly used opioid analgesic and as an induction agent in cardiac patients for its hemodynamic stability. Carotid sinus baroreceptor reflex control of HR is depressed by fentanyl. Bradycardia is more prominent with fentanyl, as it slows atrioventricular conduction. A fall in systemic vascular resistance resuts in hypotension after larger doses of fentanyl.,
The study aimed to observe whether dexmdetomidine or MgSO4 could replace fentanyl in its pharmacodynamic action.
Saraf et al. observed IV dexmedetomidine 0.6 μg/kg attenuated the pressor response during intubation with a minimal incidence of bradycardia and hypotension. Panda et al. compared the different doses of IV MgSO4 and concluded that 30 mg/kg as the optimum dose for attenuating the rise in blood pressure during laryngoscopy. Fentanyl 2 μg/kg IV, which is a routine dose, was used in attenuating pressor response during tracheal intubation.
Based on the above studies, we compared these low doses of IV dexmedetomidine 0.6 μg/kg, IV MgSO4 30 mg/kg and IV fentanyl 2 μg/kg. Low doses were used for trial to balance the benefits versus the untoward effects of these drugs but keeping the advantages of analgesia and amnesia during surgery.
No statistically significant difference was found between dexmedetomidine and fentanyl in all the hemodynamic variables but there were significant differences in hemodynamic profile when the two drugs were compared individually with MgSO4.
Heart rate dynamics
All the three drugs showed statistically increase in HR from baseline values when compared to mean value over 10 min after intubation. On intergroup comparison, M group had a significant increase in HR after giving test drugs, at induction and 3 min, 5 min after intubation.
Our study was consistent with Sharma and Parikh using a similar dose of fentanyl and found an increase in HR after intubation and a drop after intubation at 10 min. MgSO4 group showed an increase in HR after intubation. Our research results were comparable to Puri et al. (50% of 0.1 ml/kg MgSO4) and Sharma et al. (40 mg/kg MgSO4) where an increase in HR after intubation was observed.
Reddy et al. using dexmedetomidine 1 μg/kg found a statistically insignificant rise in HR after intubation. In contrast, Kharwar et al. observed that dexmedetomidine 1 μg/kg and fentanyl 2 μg/kg resulted in a statistically significant decrease in HR from baseline in the dexmedetomidine group. Saraf et al. and Jaakola et al. found significant reduction of HR with dexmedetomidine 0.6 μg/kg, which was not observed in our study.
Systolic blood pressure dynamics
There was fall in SBP in all groups after induction of anesthesia and a statistically significant fall in SBP was seen with D and F group when their mean values over 10 min were compared with their baseline values.
In the dexmedetomidine group, we observed a fall in SBP after intubation when compared to baseline. Jaakola et al. and Saraf et al. used dexmedetomidine 0.6 μg/kg and noticed a fall in SBP after intubation. Sharma and Parikh who used a similar dose of fentanyl, noticed a rise in SBP immediately after intubation and a drop at 5 and 10 min later. However, the drop in SBP in our study was found to be more than their obervation.
There was a rise in SBP at 1 min after intubation and a fall was noticed thereafter in the MgSO4 group. In the study conducted by Navid et al., the MgSO4 dose (60 mg/kg) was higher than our study and they observed a mean rise in SBP by 4.7 mmHg, whereas in our study, there was a mean fall by 2.87 mmHg from baseline after intubation. Therefore, attenuation of SBP with low dose MgSO4 (30 mg/kg) gave a better hemodynamic response in our study.
This is similar observation as with the study done by Puri et al. (50% MgSO4 in a dose 0.1 ml/kg) where a sudden rise in SBP during intubation with MgSO4 was observed.
Gogus et al. used 1 μg/kg dexmedetomidine and fentanyl 2 μg/kg and found a decrease in SBP which was almost comparable levels consistent with our study.
Diastolic blood pressure dynamics
A statistically significant decrease in DBP was observed from baseline over 10 min after intubation with dexmedetomidine and fentanyl groups and not in MgSO4. It was consistent with the study done by Gogus et al. where they observed a rise in DBP at 1 min after intubation followed by a fall in DBP at 5 and 10 min later. The rise of DBP at 1 and 3 min after intubation was insignificant statistically.
Mean blood pressure dynamics
In all three groups, we observed that there was a fall in MAP at 3, 5, and 10 min after intubation which were similarly observed in studies by Jain et al. Navid et al. observed with MgSO4 60 mg/kg a rise in MAP after intubation at 1, 2, and 4 min. Lower dosage of MgSO4 (30 mg/kg) gave a better result in our research.
No side effects of bradycardia and hypotension were observed in all groups.
The use of BIS monitor would have helped to getter better results and assessment of response after categorizing the age groups would have given further insights of these drugs. These remain the limitations of this study.
| » Conclusions|| |
We conclude that low dose of IV dexmedetomidine 0.6 μg/kg and IV fentanyl 2 μg/kg are equally effective in reducing vasopressor response related to laryngoscopy/intubation and their efficacy is more than MgSO4 (30 mg/kg). Dexmedetomidine can serve as an alternative to fentanyl in attenuating pressor response during laryngoscopy and tracheal intubation. In contrast, MgSO4 30 mg/kg showed a statistically significant increase in HR and blood pressure during laryngoscopy/intubation comparitively, so at this dose it proved ineffective.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Fox EJ, Sklar GS, Hill CH, Villanueva R, King BD. Complications related to the pressor response to endotracheal intubation. Anesthesiology 1977;47:524-5.
Reid LC, Brace DE. Irritation of the respiratory tract and its reflex effect on heart- surgery. Gynaecol Obstet 1940;70:157-62.
Derbyshire DR, Chmielewski A, Fell D, Vater M, Achola K, Smith G. Plasma catecholamine responses to tracheal intubation. Br J Anaesth 1983;55:855-60.
Jaakola ML, Ali-Melkkilä T, Kanto J, Kallio A, Scheinin H, Scheinin M. Dexmedetomidine reduces intraocular pressure, intubation responses and anaesthetic requirements in patients undergoing ophthalmic surgery. Br J Anaesth 1992;68:570-5.
Kallio A, Scheinin M, Koulu M, Ponkilainen R, Ruskoaho H, Viinamäki O, et al.
Effects of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on hemodynamic control mechanisms. Clin Pharmacol Ther 1989;46:33-42.
Taylor P. Agents acting at the neuromuscular junction and autonomic ganglia. In: Brunton LL, editor. Goodman and Gilman's the Pharmacological Basis of Therapeutics. 12th
ed. New York: McGraw Hill; 2006. p. 296-323.
Bucx MJ, van Geel RT, Scheck PA, Stijnen T. Cardiovascular effects of forces applied during laryngoscopy. The importance of tracheal intubation. Anaesthesia 1992;47:1029-33.
Stoelting RK, Hillier SC. Opioid agonists and antagonists. In: Pharmacology and Physiology in Anesthetic Practice. 4th
ed. New York: Lippincott Raven Publishers; 1999. p. 87-123.
Fakuda K. Intravenous opioid anesthetics. In: Miller's Anaesthesia. 6th
ed. Philadelphia: Elsevier; 2005. p. 392.
Saraf R, Jha M, Kumar SV, Damani K, Bokil S, Galante D. Dexmedetomidine is the ideal drug for attenuating the pressor response. Paediatr Anaesth Crit Care J 2013;1:78-86.
Panda NB, Bharti N, Prasad S. Minimal effective dose of magnesium sulfate for attenuation of intubation response in hypertensive patients. J Clin Anesth 2013;25:92-7.
Sharma N, Parikh HA. Comparative study of haemodynamic responses to intubation: fentanyl versus nalbuphine. Gujarat Med J 2014;9:48-53.
Puri GD, Marudhachalam KS, Chari P, Suri RK. The effect of magnesium sulphate on hemodynamics and its efficacy in attenuating the response to endotracheal intubation in patients with coronary artery disease. Anesth Analg 1998;87:808-11.
Sharma J, Sharma V, Ranbhushan, Guptha S. Comparative study of magnesium sulphate and esmolol in attenuating the pressor response to endotracheal intubation in controlled hypertensive patients. J Anaesthesiol Clin Pharmacol 2006;22:255-9. [Full text]
Reddy SV, Balaji D, Ahmed SN. Dexmedetomidine versus esmolol to attenuate the hemodynamic response to laryngoscopy and tracheal intubation: A randomized double-blind clinical study. Int J Appl Basic Med Res 2014;4:95-100.
Kharwar RK, Kumar M, Tiwary PK, Suwalka U, Prakash S. A comparison of intravenous dexmedetomidine v/s inj. fentanyl for attenuation of haemodynamic responses during laryngoscopy and intubation after propofol induction. NJIRM 2014;5:71-5.
Nooraei N, Dehkordi ME, Radpay B, Teimoorian H, Mohajerani SA. Effects of intravenous magnesium sulfate and lidocaine on hemodynamic variables following direct laryngoscopy and intubation in elective surgery patients. Tanaffos 2013;12:57-63.
Gogus N, Akan B, Serger N, Baydar M. The comparison of the effects of dexmedetomidine, fentanyl and esmolol on prevention of hemodynamic response to intubation. Rev Bras Anestesiol 2014;64:314-9.
Jain V, Chandak A, Ghosh A, Golhar M. Comparison of dexmedetomidine and fentanyl for attenuation of the haemodynamic response to laryngoscopy and tracheal intubation. AinShams J Anaesthesiol 2015;8:236-43.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]