|Year : 2017 | Volume
| Issue : 1 | Page : 14-18
A comparative study of oral pregabalin and oral gabapentin in the attenuation of hemodynamic response to laryngoscopy and intubation
Dhananjaya Bangalore Doddaiah, Nongthombam Ratan Singh, Nirmeen Fatima, Sanasam Sarat Singh, Heikham Kenedy Singh, Khaidem Surjit Singh
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Web Publication||17-Jan-2017|
Nongthombam Ratan Singh
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal - 795 004, Manipur
Source of Support: None, Conflict of Interest: None
Background: Laryngoscopy and intubation is a noxious stimulus, which can provoke many untoward responses, particularly in the cardiovascular system in the form of hypertension, tachycardia, and dysrhythmia, which can be detrimental in cardiovascular compromised patients. The aim of the study was to compare the efficacy of preoperative oral pregabalin and gabapentin in attenuating hemodynamic responses to laryngoscopy and intubation. Materials and Methods: One hundred and twenty adult patients undergoing elective surgery under general anesthesia were randomly allocated by computer-generated randomization into three groups of forty patients each to receive preoperatively - Group C - vitamin capsules, Group G - gabapentin 800 mg, and Group P - pregabalin 150 mg, 90 min before the scheduled surgery. Systolic blood pressure (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and heart rate (HR) were recorded at baseline, 1, 5, 10, and 15 min after intubation. Results: The increase in HR response to laryngoscopy and intubation was minimized by both gabapentin and pregabalin when compared with the control group (P < 0.05) at baseline and 1 min; however, there was no statistically significant difference between the two study groups (P > 0.05). There was statistically significant reduction in SBP, DBP, and MAP at 1 min with P = 0.026, 0.014, and 0.001 and at 5 min with P = 0.002, 0.007, and <0.001, respectively, in gabapentin group. In pregabalin group, there was a reduction in SBP, DBP, and MAP at 1 min following intubation with P < 0.001, <0.001, and <0.001 and at 5 min with P = 0.001, <0.001, and <0.001, respectively. Conclusion: Oral pregabalin and gabapentin in the present study attenuates hemodynamic responses to laryngoscopy and intubation. There was a significant reduction in SBP, DBP, and MAP, but not the tachycardia.
Keywords: Attenuation, gabapentin, intubation, laryngoscopy, pregabalin, stress response
|How to cite this article:|
Doddaiah DB, Singh NR, Fatima N, Singh SS, Singh HK, Singh KS. A comparative study of oral pregabalin and oral gabapentin in the attenuation of hemodynamic response to laryngoscopy and intubation. J Med Soc 2017;31:14-8
|How to cite this URL:|
Doddaiah DB, Singh NR, Fatima N, Singh SS, Singh HK, Singh KS. A comparative study of oral pregabalin and oral gabapentin in the attenuation of hemodynamic response to laryngoscopy and intubation. J Med Soc [serial online] 2017 [cited 2020 May 26];31:14-8. Available from: http://www.jmedsoc.org/text.asp?2017/31/1/14/198428
| Introduction|| |
Laryngoscopy and intubation is a noxious stimulus, which can provoke untoward response in cardiovascular systems. It is associated with hypertension, tachycardia, dysrhythmias, increased circulatory catecholamines, and myocardial ischemia.  These responses are well-tolerated in healthy individuals, but it may increase the perioperative morbidity and mortality in those patients with coronary artery diseases, vascular anomalies, or intracranial diseases. 
Several techniques have been proposed to prevent or attenuate these hemodynamic responses to laryngoscopy and tracheal intubation such as deepening the plane of anesthesia,  pretreatment with vasodilators,  β-blockers,  calcium channel blockers,  and opioids.  However, there is not a single technique which can attenuate completely the stress response of laryngoscopy and intubation.
Pregabalin, a gabapentinoid compound and a (S)-3 aminomethyl-5-methylhexanoic acid, is structurally related to inhibitory neurotransmitter gamma-aminobutyric acid (GABA), but is not functionally related. It acts by decreasing the synthesis of glutamate, possessing analgesic, anticonvulsant, and anxiolytic activities. It is also effective in preventing neuropathic component of acute nociceptive pain of surgery. 
Gabapentin, a structural analog of GABA, used as an antiepileptic drug has also been shown to be effective in neuropathic pain-inhibiting calcium influx and subsequent release of excitatory neurotransmitter in pain pathways to presynaptic voltage-gated calcium channels.  Recently, gabapentin was effectively used to attenuate hemodynamic response to laryngoscopy and endotracheal intubation. ,
The study was undertaken to evaluate the efficacy of pregabalin and gabapentin in attenuating hemodynamic responses to laryngoscopy and intubation.
| Materials And Methods|| |
After obtaining approval from the Institutional Ethical Committee and informed written consent from patients, a prospective randomized, double-blind, placebo-controlled study was undertaken.
Assuming a α-value of 0.05, power of study of 0.8, the sample size was 36, and assuming a 5% drop out rate, the final sample size was rounded to forty in each group based on a previous study. 
One hundred and twenty patients of American Society of Anesthesiologists  physical status Grade I and II, 18-60 years, of either sex, scheduled for elective surgeries under general anesthesia were divided into three groups of forty patients in each group by a computer-generated randomization table.
- Group C (n = 40) - Vitamin B capsules
- Group G (n = 40) - 800 mg of gabapentin (capsule gabapentin)
- Group P (n = 40) - 150 mg of pregabalin (capsule pregabalin).
Patients with a history of drug allergy to pregabalin or gabapentin, physically dependent on narcotics, cerebrovascular, neurologic, respiratory, and ischemic heart disease, renal and hepatic dysfunction, hypertension, diabetes mellitus, patients on β-blockers, anti-depressants, anti-anxiety, anti-convulsants or anti-psychotics, and anticipated difficult intubation were excluded from the study.
The patients were kept nil orally after 10 pm and received tablet alprazolam 0.5 mg and tablet ranitidine 300 mg as premedication on the night before surgery. On the morning of the surgery, the patients were given oral pregabalin 150 mg, oral gabapentin 800 mg, or oral placebo capsules according to their respective groups 90 min before surgery.
Upon arrival in the operating room, intravenous (IV) access was secured with 18-gauge IV cannula and all were given IV fluids. Patients were premedicated with injection glycopyrrolate 5 μgm/kg, injection ranitidine 1 mg/kg, and injection ondansetron 0.08 mg/kg 30 min before the induction of anesthesia.
Baseline parameters such as pulse rate, systolic blood pressure (SBP), diastolic BP (DBP), mean BP, oxygen saturation, and electrocardiogram were recorded.
A uniform anesthetic technique was used in all the three groups, namely, after 3 min of preoxygenation with 100% oxygen, anesthesia was induced with IV propofol (2 mg/kg) till the loss of eyelash reflex; laryngoscopy and intubation was facilitated with IV injection suxamethonium (2 mg/kg) and the airway was secured. Anesthesia was maintained with 60% nitrous oxide in oxygen along with isoflurane 0.8 volume % (~1.0 minimum alveolar concentration with nitrous oxide) + IV injection atracurium (0.5 mg/kg as loading dose and 0.02 mg/kg as maintenance dose) and mechanically ventilated to maintain normocapnia (EtCO 2 between 35 and 40 mm Hg).
During laryngoscopy and endotracheal intubation, heart rate (HR), SBP, DBP, and mean arterial BP changes were recorded at baseline, 1, 5, 10, and 15 min.
All the parameters recorded were entered in excel sheet. Analysis of variance has been used to find the significance of study parameters between three or more groups of patients and post hoc Tukey test has been used to find the pairwise significance between the groups. The statistical software, namely Statistical package for social sciences for windows (SPSS) version 21.0 (Armonk, NY: IBM corp.) was used for the analysis of the data. Microsoft word and Excel have been used to generate graphs, tables, etc.
| Results|| |
The groups were comparable with respect to age and sex. There were no significant differences in demographic profile among the three groups [Table 1]. As shown in [Figure 1], in gabapentin group, there was a statistically significant reduction in HR at baseline and 1 min (P < 0.005, P < 0.04, respectively) as compared to control group. In pregabalin group, there was a statistically significant reduction in HR at baseline, 1, and 5 min (P < 0.001, P < 0.01, and P < 0.05, respectively) as compared to control group. However, there was no statistically significant difference between the two study groups at all-time intervals (P > 0.05). The mean arterial BP at 1, 5, and 10 min interval after intubation was low in the pregabalin group with a statistically significant P value (P < 0.01). When compared to control group, reduction in the mean arterial BP at 1 and 5 min was statistically significant (P < 0.001 at 1 and 5 min) in the gabapentin group. There was also reduction in the mean arterial BP at 1, 5, 10, and 15 min in pregabalin group as compared to control group (P < 0.01 at 1 and 5 min, 0.002 at 15 min). There was a statistically significant decrease in mean arterial pressure (MAP) in pregabalin group when compared to gabapentin group at 1 and 10 min with P < 0.06 and P < 0.07, respectively.
|Figure 1: The comparison of the mean heart rate ± standard deviation and mean arterial pressure ± standard deviation at different time intervals|
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The mean SBP was lesser in the pregabalin group at 1, 5, and 10 min as compared to control group and it was statistically significant (P < 0.001, P < 0.001, and P < 0.004, respectively). There was a statistically significant lesser SBP in gabapentin group at 1 and 5 min as compared to control group (P < 0.02 and P < 0.002, respectively). There was no statistically significant difference in SBP noted between the pregabalin and gabapentin group (P = 0.137). There was statistically significant reduction in DBP in gabapentin group at 1 and 5 min as compared to control group (P < 0.01 and P < 0.007, respectively). There was a decrease in DBP in pregabalin group when compared to control group at 1, 5, 10, and 15 min, and it was statistically significant (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively). Between gabapentin and pregabalin groups, statistically lower DBP was seen at 1 min after intubation in the pregabalin group with P < 0.03 [Figure 2].
|Figure 2: The comparison of the mean systolic blood pressure ± standard deviation and mean diastolic blood pressure ± standard deviation at different time intervals|
Click here to view
| Discussion|| |
Laryngoscopy and endotracheal intubation elicits reflex hemodynamic response. This response is due to stimulation of mechanoreceptors over the pharyngeal wall, epiglottis, and vocal cord, which, in turn, leads to sympathoadrenal activity. ,
Several techniques have been proposed to attenuate the hemodynamic responses following laryngoscopy and intubation such as deepening the plane of anesthesia,  premedication with drugs such as IV lignocaine,  nitroglycerine,  β-blockers,  calcium channel blockers  and opioids,  topical application of local anesthetics, and infiltration of nerve with local anesthetics (nerve blocks). However, no single technique was satisfactory.
In our study, the groups were comparable with respect to their demographic variables and their baseline values of HR, SBP, DBP, and MAP. There was a significant increase in HR, SBP, DBP, and MAP compared to baseline in all groups following laryngoscopy and intubation.
Gupta et al.  used pregabalin as a premedicant in the attenuation of hemodynamic response to laryngoscopy and intubation. In their study, they administered oral pregabalin 150 mg 60-75 min before surgery. Their study showed an increase in HR and MAP in both groups, but were significantly lower in pregabalin group at 1 min following intubation compared to control group (P < 0.007).
In a study by Salman et al.,  sixty patients were given oral placebo and oral pregabalin 150 mg 1 h prior to surgery. There was a significantly lower SBP, DBP, and MAP in pregabalin group (P = 0.002, P = 0.031, and P = 0.011, respectively) compared to placebo group.
In our study, we used pregabalin at a dose of 150 mg 90 min prior to intubation. Pregabalin was found to attenuate the rise in HR and MAP at 1 and 5 min after intubation compared to control group. Near-stable hemodynamic variables in the present study were an indication of adequate analgesia and sedation with oral pregabalin. This correlates with studies done by Gupta et al.,  Salman et al.,  and Sundar et al. 
In our study, pregabalin 150 mg group showed a significant reduction in SBP at 1, 5, and 10 min following intubation compared to control group with P = 0.001, P = 0.001, and P = 0.003, respectively. In pregabalin group, there was also a significant reduction in DBP and MAP at 1, 5, 10, and 15 min as compared to control group. This correlates with studies done by Rastogi et al.  and Gupta et al.  Several mechanisms may contribute to this beneficial effects of pregabalin. The effect of pregabalin on hemodynamic response to laryngoscopy and intubation may be explained by its inhibitory effects on membrane voltage-gated calcium channels. Pregabalin binds potently and selectively to alpha 2 delta subunit of hyperexcited voltage-gated calcium channels and inhibits the release of several neurotransmitters such as glutamate, noradrenaline, and substance P.  It does not interact with GABA receptors. However, only few data are available in literature regarding the effect of pregabalin on cardiovascular system.
Memis et al.  in their randomized study compared the effect of gabapentin 400 mg versus 800 mg for MAP and HR attenuation following tracheal intubation and compared it with a placebo. According to their study, patients receiving placebo and 400 mg gabapentin showed a significant increase in blood pressure and HR following tracheal intubation compared to baseline levels. There was a significant decrease in HR and MAP in the group receiving 800 mg gabapentin at 1, 3, 5, and 10 min after intubation compared to the placebo group and 400 mg gabapentin group.
In our study, we used oral gabapentin 800 mg 90 min prior to intubation. We found that gabapentin attenuates the rise in SBP, DBP, and MAP at 1 and 5 min after intubation. This result correlates with the studies done by Shreedhara et al.,  Memis et al.,  and Neogi et al.  We observed a reduction in HR in gabapentin group at 1 min after intubation compared to control group with P = 0.047, which is statistically significant and this result correlates with that of Bafna et al.,  Montazeri et al.,  and Iftikhar et al.  Gabapentin is a second-generation antiepileptic which is structurally similar to GABA (gamma-amino butyric acid). It is found to be an effective preoperative anxiolysis.  The mechanism by which gabapentin attenuates the pressor response to laryngoscopy and intubation is not fully known. One of the proposed mechanism is by inhibition of membrane voltage-gated calcium channels, thus acting similar to calcium channel blockers or by decreasing the synthesis of excitatory neurotransmitter glutamate. 
In addition, there was some reduction in HR, SBP, DBP, and MAP between gabapentin and pregabalin groups, but it was not statistically significant. This may be because of similar mechanism of action of pregabalin and gabapentin on membrane voltage-gated calcium channels.
No patient of either group suffered from bradycardia, hypotension, or postoperative respiratory depression. Sedation was not scored in the present study.
Although we restricted our laryngoscopy period to <15 s, we did not measure the duration of laryngoscopy
We did not measure the stress mediators (catecholamine levels) in plasma. However, correlation of catecholamine levels with stress response to intubation is controversial in literature
In the inclusion criteria, the cases could have been narrowed to a specific surgical procedure such as laparoscopic or open cholecystectomy and thyroid surgeries only
Sedation was not scored in our study; this can be considered as a limitation.
| Conclusion|| |
Both oral gabapentin 800 mg and pregabalin 150 mg administered as a premedicant are safe and effective measures in attenuating the hemodynamic responses to laryngoscopy and intubation. However, further studies with different doses and timing of the study drugs need to be assessed.
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Conflicts of interest
There are no conflicts of interest.
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