|Year : 2015 | Volume
| Issue : 1 | Page : 35-39
Attenuation of hemodynamic response to laryngoscopy and intubation using intravenous fentanyl and esmolol: A study
Sathappan Karuppiah, Nongthombam Ratan Singh, Khulem Maniram Singh, Takhelmayum Hemjit Singh, Ashem Jack Meitei, Hemona Sinam
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Web Publication||17-Jun-2015|
Dr. Nongthombam Ratan Singh
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal - 795 004, Manipur
Source of Support: None, Conflict of Interest: None
Background: The present study was designed to compare the effect of intravenous fentanyl and esmolol for the attenuation of hemodynamic responses to laryngoscopy and intubation. Materials and Methods: Ninety patients undergoing elective surgical procedures were allocated into three groups viz., Group I (control): Identical volume of normal saline intravenously (IV) 3 min before induction; Group II (fentanyl): Injection fentanyl 2 mcg/kg IV 3 min before induction; Group III (esmolol): Injection esmolol 0.2 mg/kg i.v 3 min before induction. The heart rate and arterial blood pressure changes were monitored at the following time intervals: Before intubation, at intubation, and after intubation at different time intervals. The results were tabulated and statistically analysed and P ≤ 0.05 was considered significant. Results: Maximum rise in systolic blood pressure was observed at the post-intubation first minute, i.e., 22% (163.60 ± 16.25); 15% (144.13 ± 24.72); and15% (153.80 ± 24.75) in the Group I, II, and III from the baseline, respectively. Changes in the systolic blood pressure (SBP) was found to be minimum with fentanyl and esmolol groups when compared to the control group (P < 0.001). The diastolic blood pressure and mean arterial pressure changes was significant between fentanyl and esmolol groups with the control but not between esmolol and fentanyl. Group II showed better control of heart rate during laryngoscopy and intubation at the first min after intubation compared to other groups (P < 0.05). Conclusion: Fentanyl 2 μg/kg bolus or esmolol 0.2 mg/kg bolus 3 min before induction significantly attenuates the hemodynamic response to laryngoscopy and intubation better than control group.
Keywords: Attenuation, Esmolol, Fentanyl, Hemodynamic response, Intubation, Laryngoscopy
|How to cite this article:|
Karuppiah S, Singh NR, Singh KM, Singh TH, Meitei AJ, Sinam H. Attenuation of hemodynamic response to laryngoscopy and intubation using intravenous fentanyl and esmolol: A study. J Med Soc 2015;29:35-9
|How to cite this URL:|
Karuppiah S, Singh NR, Singh KM, Singh TH, Meitei AJ, Sinam H. Attenuation of hemodynamic response to laryngoscopy and intubation using intravenous fentanyl and esmolol: A study. J Med Soc [serial online] 2015 [cited 2019 Dec 14];29:35-9. Available from: http://www.jmedsoc.org/text.asp?2015/29/1/35/158931
| Introduction|| |
The hemodynamic response to laryngoscopy and tracheal intubation in most patients are transient, highly variable, and probably of little consequences but may have adverse effects like arrhythmias, myocardial ischemia, left ventricular failure, increased intracranial pressure, and rupture of cerebral aneurysm on patients with pre-existing cardiovascular disease and cerebrovascular disease. ,
Attempts to attenuate the catecholamine-induced hemodynamic responses to laryngoscopy and intubation have been made using a variety of pre-treatments ranging from topical anaesthetisation of the larynx to administration of several classes of drugs. Each technique has disadvantages, the most obvious being that prevention often outlasts the stimulus.
Among the beta-blocking agents, esmolol hydrochloride an ultra-short-acting beta blocker, with cardio selective properties having an elimination half-life of 9 min and distribution half-life of 2 min is the choice in prevention of hemodynamic alteration following endotracheal intubation and laryngoscopy. ,
Fentanyl citrate, an opioid is a phenylpiperidine of the 4-aminopiperidine series structurally related to but not derived from pethidine in the appropriate dose, controls both heart rate and blood pressure responses. , However, complex respiratory depression and truncal rigidity are frequent accompaniments. 
The present study was designed to compare the effect of intravenous fentanyl citrate and intravenous esmolol hydrochloride for the attenuation of hemodynamic responses to laryngoscopy and intubation.
| Materials and Methods|| |
After obtaining approval from the institutional ethics committee and written informed consent from the patients, the study was carried out in a tertiary care teaching hospital at Imphal during 2011 to 2013. Ninety patients of American Society of Anaesthesiologists (ASA) grade I and II aged between 20-60 years undergoing elective surgical procedures were included in the study. Patients with anticipated difficult intubation, significant cardiac, neurological, respiratory, hepatic, renal disorders, history of drug allergy, and unwilling patients were excluded. The study was a randomized controlled double blind study based on the study of Gupta and Tank,  with alpha error 0.05% and power 0.8, and a computer-generated sample size of 30 patients each was taken for the three groups: Group I (control group): Patient received identical volume of normal saline intravenously(IV) 3 min before induction; Group II (fentanyl group): Patient received injection fentanyl citrate 2mcg/kg IV, 3 min before induction; and Group III (esmolol group): Patient received injection esmolol hydrochloride 0.2 mg/kg IV3 min before induction. All the patients were kept overnight fasting and premedicated with injection glycopyrrolate 0.004mg/kg intramuscular (im) 1 h prior to induction of anaesthesia. On arrival at the operation theatre, baseline heart rate (HR), non-invasive blood pressure(NIBP), continuous electrocardiogram (ECG), and peripheral saturation of oxygen (SpO 2 ) were recorded with the help of multichannel cardiac monitor (Cardiocap Datex, Helsinki, Finland).The study drug was prepared in a 5 ml syringe separately by another anaesthesiologist not involved in the study and identical volumes of study drugs were given.
After administration of the study drug, all the patients were preoxygenated for 3 min, anesthesia was induced with 1% propofol 3mg/kg body weight and endotracheal intubation was facilitated with injection succinylcholine 1.5 mg/kg body weight. Anesthesia was maintained with balanced technique of nitrous oxide 60%, oxygen 40%, systemic analgesic, isoflurane 1%, and injection atracurium besylate 0.5 mg/kg. At the end of the surgery, patients were reversed with injection neostigmine 0.05 mg/kg and injection glycopyrrolate 8 μg/kg. Patients were extubated after the return of airway protective reflex. The heart rate, arterial blood pressure, and electrocardiography (ECG) changes were observed at the following time intervals.
- Before intubation-baseline, after the study drug administration at 1min, 2min, 3 min.
- At intubation.
- After intubation at 1 min, 2 min, 3 min, 4 min, and 5 min.
The results were tabulated and statistically analysed by Statistical Package for Social Sciences (SPSS) version 16, using the Chi-square test for categorical variable and analysis of variance (ANOVA) test for continuous variables and P ≤ 0.05 were considered statistically significant.
| Results|| |
There was no significant difference in the demographic profile amongst the groups regarding age, sex, and weight of the patients [Table 1].
Increase in systolic blood pressure was observed in all the groups from baseline but the maximum rise of systolic blood pressure was observed at post-intubation first minute which was 22% (163.60 ± 16.25), 15% (144.13 ± 24.72), and 15%(153.80 ± 24.75) in the groups I, II, and III respectively as shown in [Figure 1]. These changes were observed throughout the entire time interval and were minimal with group II (P < 0.001) and group III (P < 0.001) when compared to group I. However, there were no differences between group II and III at all time intervals. The maximum rise of diastolic blood pressure in Group I, II and III at 1 st minute after intubation was 31% (104.07 ± 16.00), 15% (92.50 ± 14.99), and 15% (98.87 ± 19.49), respectively, from the baseline (P < 0.05).
|Figure 1: Showing the comparison of the mean SBP ± SD and mean DBP ± SD at different time intervals|
Click here to view
As shown in [Figure 2], Group II had better control over increase in heart rate (P < 0.05) during laryngoscopy and intubation, i.e., 15% from base line at the first min after intubation as compared to Group I (22%) and III (20%). The heart rate returned to baseline at about fifth min after intubation in Group II unlike normal saline and esmolol. Significant difference was observed between Groups II and III at the post intubation fourth in (86.47 ± 14.82 vs95.47 ± 14.73), fifth in (84.4 ± 14.18 vs 93.97 ± 14.35) (P < 0.05). Mean arterial blood pressure (MAP) increased after laryngoscopy and intubation and the maximum rise was observed at after intubation first min, after that it again fell below the baseline at the fifth minute after intubation. However, it was well-controlled and a minimal rise was seen in Group II 15% (P < 0.001) and Group III (20%)(P < 0.001) when compared to control group (22%). MAP changes were significant between the Groups II and III with Group I but not between Group II and III [Figure 2].
|Figure 2: Showing the comparison of the mean HR ± SD and mean MAP ± SD at different time intervals |
Click here to view
| Discussion|| |
Various methods and technique have been used to attenuate the response to laryngoscopy and endotracheal intubation. It ranges, ranging from topical application of local anaesthetics, infiltration of nerve blocks, various drugs, and techniques; ,, however, no single technique or drug was satisfactory. Out of the narcotics, intravenous administration of fentanyl 1 μg/kg was better than alfentanil 10 μg/kg, remifenatanil 1 μg/kg, sufenatanil 0.1 μg/kg administered 3 minutes before induction in controlling the cardiovascular response to intubation as studied by Mireskandari et al. 
It is believed that fentanyl suppresses the hemodynamic response by increasing the depth of anesthesia and decreasing sympathetic discharge.  A low dose of fentanyl was employed in the present study because large dose of fentanyl often leads to muscular rigidity, bradycardia, respiratory depression, nausea, and vomiting. 
Adachiet al.  in their study concluded that 2 μg/kg fentanyl bolus dose effectively suppresses the hemodynamic response to both laryngoscopy and endotracheal intubation. Optimal time of injection fentanyl for blunting the hemodynamic response is 5 min before induction; on the contrary in our study we gave 3 minutes before induction.  Among the β-blockers, ultra-short-acting-like esmolol owing to its unique pharmacokinetic behaviour,  it is well-suited for controlling cardiovascular response to tracheal intubation by continuous infusion as studied by Liu et al. 
Ghaus et al. studied the effect of infusion of esmolol 300 μg/kg/min as bolus for 4 min before induction and 200 μg/kg/min for the next 6 min for maintenance during intubation found to have better control over hemodynamic response. Alternative to infusion, high bolus dose of esmolol ranging from 0.5 mg/kg to 5 mg/kg has been used in many studies. ,,
Singhal et al.  studied about the timing of esmolol injection for attenuating the hemodynamic response to laryngoscopy and intubation and they concluded that esmolol 1.5 mg/kg single intravenous bolus given 3 min before induction was very effective when compared to 90 s and 6 min before induction. However, in the present study we gave the study drugs 3 min before induction.
In our study, Group II showed better control of increased heart rate during laryngoscopy and intubation, maximum about 15% from the baseline at the first min after intubation as compared to control group, i.e.,22% (P < 0.001). The heart rate to the baseline at about 5 minute after intubation in group II which is almost similar to a study by Channaiah et al. 
On the contrary, Helfman et al.  did not find attenuation with either 200 mg lignocaine, 200 μg/kg fentanyl, however they intubated 2 min after the study drug was given. In our study we have given our study drug 3 min before induction. Maximum increase in the heart rate during/after intubation were similar in placebo (44 ± 6%), lignocaine (51 ± 10%), fentanyl (37 ± 5%), but lower in esmolol (19 ± 4%) with (P < 0.005).
In our study, Group III also maintained heart rate response to laryngoscopy and intubation better than Group I in the entire time interval. The heart rate was maintained above the baseline even after 5 min post-intubation in both the groups. However, the esmolol-controlled pressor response (heart rate) better than control group (P < 0.005), which was in accordance with Bostan et al. 
A comparison of heart rate changes between Group II and III did not yield any statistically significant difference between them in the present study for the first three minutes after intubation from baseline, but in fourth and fifth min after intubation fentanyl have a better control than esmolol(P < 0.05)Again, these results were opposed by Gupta, Tank  who found that esmolol shows significant attenuation than fentanyl in all the time interval when compared to fentanyl(P < 0.05).This maybe because they used esmolol 2 mg/kg which is ten times more than the present study.
Increase in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was there at all time intervals and maximum at post intubation first min which is in accordance with Begum et al.  who also reported that maximal response is at first min after intubation. The maximum rise of SBP and DBP in fentanyl group at first min after intubation was 15% (144.13 ± 24.72) and 15% (92.50 ± 14.99) respectively from the baseline as compared to control group SBP 22% (163.60 ± 16.25) and DBP 31% (104.07 ± 16.00) (P < 0.05).Group II returned both SBP and DBP to below baseline causing 10% reduction (112.13 ± 16.05) and 11% (71.90 ± 13.96) from baseline as compared to Group I, showing 3% reduction (131.77 ± 15.48) and 7% increase (85.57 ± 9.49) in DBP from baseline (P < 0.001).Similar results have been shown by Channaiah et al.  and Eberto et al.  Fentanyl decreases the SBP, DBP, and MAP significantly below the base line (P < 0.05), while these pressure were either retained at or elevated slightly above the control group in esmolol group. In these doses, heart rate response to laryngoscopy was more effectively blocked by the fentanyl while esmolol retained perfusion pressure, like our study which shows that fentanyl effectively blocks cardiovascular response to laryngoscopy and intubation.
In our study, Group III had maximum rise of SBP and DBP at first min after intubation and is about 20% and 22% from baseline as compared to 22% and 31% in Group I. There was no statistically significant difference between the groups at post-intubation 1 min (P>0.05) but at other time intervals, esmolol significantly controlled the pressor response which is comparable to Miller et al.  However, they observed that incidence of hypotension SBP <100 mmhg was 25% in E100 and 32% in E200 group and sustained hypotension was even observed up to 5-10 minutes. On the contrary, we did not observe any incidence of hypotension in our study which could be because of the esmolol dose which was 0.2 mg/kg.
In our study, it was observed that fentanyl was better than esmolol in maintaining blood pressure through all the time but it is not statistically significant between them (P > 0.05). Similarly, Samchung et al.  observed that there is no difference between esmolol and fentanyl in attenuating pressure response but both were better than control group (P < 0.05).They elaborated that drugs administered alone was not effective as giving them together (fentanyl and esmolol) which effectively suppresses the response (P < 0.001).
In our study, maximal effective rise of MAP from baseline at 1 st minute after intubation were 21%(123.90 ± 15.25) in group I,15% (110.10 ± 16.29) in group II, and 22% (117.97 ± 18.65) in group III respectively. However, returning of MAP to baseline was well-achieved in Group II and III at the 5 th minute after intubation when compared to control group (P < 0.05). There was no significant difference between Groups II and III regarding MAP (P > 0.05).
Bensky et al.  used esmolol 0.2 mg/kg and 0.4 mg/kg bolus before induction and compared. The findings of their study may be favourably compared with our study as both esmolol 0.2 mg/kg and 0.4 mg/kg were partially effective in attenuating the response. They concluded that increase in heart rate by esmolol 0.4 mg/kg was found to be <20% as compared to 40% in saline group (P < 0.05). Esmolol 0.4mg/kg significantly blunted the MAP of the subjects like 12% increase at 30 s as compared to 28% in normal saline.
Esmolol 200 μg/kg usually an infusion dosage for control of pressor response but here we used as single bolus dose 3 min before induction. So, further studies need to be carried out to determine the lowest possible effective bolus dose of esmolol in attenuating the hemodynamic response to intubation and laryngoscopy.
| Conclusion|| |
From the present study, we conclude that in patients with no measures/drugs to attenuate hemodynamic response to laryngoscopy and intubation, there will be a maximum rise in heart rate, SBP, DBP, and MAP when compared with pre-induction value. Fentanyl 2 μg/kg bolus or esmolol 0.2 mg/kg bolus 3 minutes before induction significantly attenuates the hemodynamic response to laryngoscopy and intubation better than control group.
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[Figure 1], [Figure 2]