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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 3  |  Page : 164-170

Comparison of haemodynamic responses to direct laryngoscopy and intubation with gabapentin versus placebo


Department of Anaesthesiology and Critical Care, S. V. Institute of Medical Sciences, Tirupathi, Andhra Pradesh, India

Date of Submission06-Dec-2019
Date of Acceptance27-Feb-2020
Date of Web Publication27-Oct-2020

Correspondence Address:
M Hanumantha Rao
Dean and Senior Professor, Department of Anaesthesiology and Critical Care, Sri Venkateswara Institute of Medical Sciences, Tirupathi, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCSR.JCSR_123_19

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  Abstract 


Background: Laryngoscopy and tracheal intubation initiate tremendous changes in heart rate (HR) and blood pressure which could be associated with deleterious consequences in susceptible individuals.
Methods: The effect of gabapentin on the haemodynamic responses to laryngoscopy and intubation in adults undergoing elective non-cardiac surgeries was investigated in the present study. Sixty adult patients of the American Society of Anaesthesiologists Grade I aged between 18–65 years and scheduled for different types of elective non-cardiac surgeries under general anaesthesia were randomly allocated to receive gabapentin 1200 mg or placebo capsules, at 6 h intervals starting the evening before surgery. After standard routine induction, succinylcholine was used to facilitate intubation. HR, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were recorded before and after the administration of the induction agent, immediately after laryngoscopy and intubation and at 1, 3, 5 and 10 min thereafter.
Results: Patient characteristics were similar in both the groups. When compared to placebo group, Gabapentin group showed significantly lower HR (at post-induction, 0, 1 and 3 min; P < 0.05), SBP (at 0, 1 and 3 min; P < 0.05), DBP (at 0 and 1 min, P < 0.05) and MAP (at 0, 1 and 3 min, P = 0.05) after laryngoscopy and intubation.
Conclusions: Gabapentin, under the present study design, attenuated the pressor response to laryngoscopy and intubation in terms of HR, SBP, DBP and MAP in patients undergoing elective non-cardiac surgeries.

Keywords: Gabapentin, intubation, laryngoscopy, pressor response


How to cite this article:
Subhadra PJ, Nagaraj G, Rao M H. Comparison of haemodynamic responses to direct laryngoscopy and intubation with gabapentin versus placebo. J Clin Sci Res 2020;9:164-70

How to cite this URL:
Subhadra PJ, Nagaraj G, Rao M H. Comparison of haemodynamic responses to direct laryngoscopy and intubation with gabapentin versus placebo. J Clin Sci Res [serial online] 2020 [cited 2020 Nov 30];9:164-70. Available from: https://www.jcsr.co.in/text.asp?2020/9/3/164/298950




  Introduction Top


The reflex circulatory response to direct laryngoscopy and tracheal intubation was first described by King et al.[1] These responses include hypertension, tachycardia and dysrhythmias due to catecholamine release.[2] Such pressor response does not have consequences in normal patients (American Society of Anaesthesiologists Physical Status Grade I [ASA I]) but may be associated with myocardial ischemia, myocardial failure in susceptible patients with coronary artery disease, valvular heart disease, geriatric and critically ill patients and cerebral haemorrhage in head injury patients with raised intracranial tension. Thus, these transient haemodynamic changes can alter the mortality and morbidity.

Various techniques and drugs were used to attenuate or abolish these responses, ranging from pre-medication with beta-blockers,[3] calcium channel blockers,[4] vasodilators such as nitroglycerine,[5] using additional doses of narcotics,[6] deepening anaesthesia before laryngoscopy,[7] gentle and single attempt laryngoscopy, repeated injections of intravascular induction agents, increasing the concentration of the inhalational agents (e.g., sevoflurane), preservative free lignocaine intravenously 90 s before intubation[8] and intravenous[9] or oral clonidine 2 h prior to intubation.[10]

Gabapentin was introduced as an antiepileptic,[11] well tolerated with minimal side effects as compared with other antiepileptics such as carbamazepine. It also proved to be effective in controlling neuropathic pain.[12],[13] More recently, gabapentin has been used in randomised controlled trials to treat acute post-operative pain[14],[15] and to reduce the post-operative opioid requirements. While performing these studies with gabapentin, it was observed that some patients were haemodynamically stable. Other studies have shown that gabapentin was able to attenuate these pressor responses usefully, given by different protocols.[16],[17],[18]

The present study was conducted to investigate the effect of gabapentin on the changes in blood pressure and heart rate (HR) observed during laryngoscopy and tracheal intubation when given as an oral pre-medication in three divided doses on the night before and morning of surgery.


  Material and Methods Top


A prospective, double-blind, randomised, placebo controlled study was conducted after obtaining approval from the Institutional Ethics Committee, and written informed consent from all the patients prior to recruitment into the study. Sixty adult patients of ASA Grade I[19] within the age group of 18–65 years and scheduled for different types of elective non-cardiac surgeries (e.g., neurosurgery, urology, plastic surgery, general surgery and surgical gastroenterology) under general anaesthesia were included in the study. Using computer-generated random number sequence and sealed opaque envelope technique prior to the initiation of the study, these sixty patients were allocated into two groups (Group G and Group P) of 30 each to receive either gabapentin or placebo as oral pre-medication.

Patients with anticipated difficult intubation; ASA physical status II or greater; hiatus hernia and gastroesophageal reflux disease; body weight more than 20% of the ideal body weight; age >65 years and younger than 18 years; history of consumption of antihypertensives, sedatives, hypnotics, antidepressants and drugs with effect on the nervous system, except those allowed by the study protocol (e.g., sedation by gabapentin is acceptable for the study), were excluded prospectively. Those patients in whom laryngoscopy took >15 s was of more than Grade 1 by Cormack–Lehane grading[20] and more than one attempt was required were excluded retrospectively.

Gabapentin 400 mg or placebo capsules were administered at 18:00 h and 24:00 h on the day before surgery and at 06:00 h on the morning of surgery. Computer-generated random numbers, envelope labelling and group allocation were done by an anaesthesiologist who is not aware of the study protocol and did not participate in the study. The same anaesthesiologist had also distributed the capsules to the patients according to the group allocation. Placebo capsules were taken from the manufacturer without drug inside.

All patients were visited and evaluated on the previous day of surgery. The anaesthetic procedure and modified Allen's test[21] were explained to the patient and were done during this visit and informed consent was obtained. Only those patients who were first on theatre list were included into the study, so that peak effect of the drug is coinciding with the induction and intubation time (2–3 h after the final or third dose). Patients were fasting for 8 h prior to surgery and capsule omeprazole 40 mg orally was given 1 h before dinner on the night before surgery.

On arrival into the operating room, non-invasive monitoring was initiated with electrocardiogram, pulse oximetry, end-tidal capnography (EtCO2) and non-invasive blood pressure measurement. Peripheral intravenous access was secured with 18G cannula and infusion of ringer lactate was started. Under local anaesthesia, the left radial artery was cannulated with a 20G arterial cannula for invasive monitoring. Baseline HR, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were recorded.

All patients received metoclopramide 10 mg intravenously, 10 min before the induction of anaesthesia. After pre-oxygenation for 3 min, all patients were given midazolam 0.02 mg/kg body weight, fentanyl 1 μg/kg, defasciculating dose of vecuronium 0.01 mg and thiopentone sodium 5 mg/kg. Succinylcholine was used to facilitate the intubation.

After 60 s of mask ventilation with 100% oxygen, laryngoscopy was performed with appropriate-sized curved Mcintosh blade and patients were intubated with appropriate-sized cuffed endotracheal tubes. Cuff was inflated gradually by simultaneously feeling for air leak. Endotracheal tube was fixed after confirming the position by auscultation and EtCO2 graph.

All intubations were performed by an experienced anaesthesiologist with at least >3 years of experience, and the duration of laryngoscopy and intubation was recorded. Those cases in which laryngoscopy was of Grade I according to the Cormack–Lehane classification[20] [Table 1] were included in the study Their. Those cases where laryngoscopy and intubation took >15 s were also excluded from the study. Systolic arterial pressure, diastolic arterial pressure, MAP and HR were recorded before and after the administration of the induction agent, immediately after laryngoscopy and intubation (0 min), 1, 3, 5 and 10 min thereafter.
Table 1: Cormack–Lehane classification[20]

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Statistical analysis

Continuous variables are presented as mean ± standard deviation. All categorical variables were analysed using Chi-square test. Haemodynamic changes within each group at different time intervals and also between two groups were analysed using repeated-measures ANOVA test with Bonfernii post hoc test wherever appropriate. P < 0.05 was considered to be statistically significant. Data were analysed using Statistical Package for Social Sciences (SPSS) version 16 (SPSS Inc. Chicago).


  Results Top


Patient characteristics such as age, sex and body weight and mean duration of laryngoscopy were comparable in both the groups without any statistical significance [Table 2].
Table 2: Demographic data

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The differences in HR at baseline, post-induction, 0 min, 1 min and 3 min after laryngoscopy and intubation were statistically significant (P = 0.045, 0.009, 0.0016, 0.004 and 0.021, respectively). However, difference in HR at pre-induction, 5 min and 10 min after laryngoscopy and intubation between the two groups was not statistically significant (P = 0.069, 0.064 and 0.14, respectively) [Table 3]. There was a difference in the values of HR within each group over the time which is statistically significant (F ratio with duration of time = 22.223; P = 0.001 in gabapentin group and 38.065, P = <0.001). The difference over the time between the groups was statistically significant (F ratio between groups of patients is 7.03; P = 0.01). The interaction F ratio calculated between F ratio with a duration of time and between groups of patients was 2.009 with a P = 0.053 which was not significant [Table 3].
Table 3: Comparison of heart rate between the groups

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SBP at 0 min, 1 min and 3 min after laryngoscopy and intubation was found to be statistically significant between the two groups of patients with P < 0.001, 0.001 and 0.02, respectively [Table 4]. At other time points, the difference was not statistically significant. There was a statistically significant difference in the values of SBP within each group over the time (31.878, P < 0.001 in gabapentin group and 52.150, P < 0.001 in placebo group, i.e., F ratio over the time). The F ratio between groups of patients was significant (7.184) with a P = 0.010. Interaction F ratio calculated between F ratio with duration of time and between groups of patients was also statistically significant (interaction F ratio = 13.41; P < 0.001).

DBP at 0 min and 1 min after laryngoscopy and intubation was found to be statistically significant (P = 0.0025 and 0.0003, respectively) [Table 5]. There was a statistically significant difference in the values of DBP both within each group over the time (F ratio with a duration of time = 22.155, P < 0.001 in gabapentin group and 41.697 with a P < 0.001 in placebo group). The F ratio between groups of patients was 0.892 and it was not significant (P = 0.349). Interaction F ratio calculated between F ratio with duration of time and between groups of patients was also statistically significant (Interaction F ratio = 10.65; P < 0.001).
Table 4: Comparison of systolic blood pressure between the groups

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Table 5: Comparison of diastolic blood pressure between the groups

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MAP at 0 min, 1 min and 3 min after laryngoscopy and intubation was statistically significant between two groups of patients (P = 0.0002, <0.001 and 0.04, respectively) [Table 6]. There was a statistically significant difference in the values of MAP both within each group over the time (F ratio with a duration of time = 30.573 with P < 0.001 in the gabapentin group and 52.525 with P < 0.001 in placebo group). F ratio between groups of patients was 3.569 and was not statistically significant. Interaction F ratio calculated between F ratio with duration of time and between groups of patients was also statistically significant (interaction F ratio = 13.55; P < 0.001).
Table 6: Comparison of mean arterial blood pressure between the groups

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  Discussion Top


The cardiovascular responses to laryngoscopy and tracheal intubation are well known and linked with increasing catecholamine blood levels.[11] Shribman et al. found that laryngoscopy alone or followed by tracheal intubation increases arterial pressure and catecholamine levels, while intubation significantly increases HR. Our results are consistent with its findings, but we did not measure catecholamine levels.

Several techniques have been proposed to attenuate such responses. Nitroglycerin[5] administered intranasally attenuated the hypertensive response to laryngoscopy and intubation, but tachycardia was observed in both the nitroglycerin and the control group. Furthermore, topical lignocaine[22] spray applied before or after induction of anaesthesia prevented the increase in mean arterial blood pressure but had no effect on the HR. Beta-blockers[8],[23],[24] and calcium channel blockers[25],[26],[27] have also been used successfully to prevent the haemodynamic responses to tracheal intubation. Drugs with rapid onset and short duration of action similar to the beta-blocker esmolol and the opioid remifentanil are particularly useful for the induction–intubation period. The most recent studies regarding the prevention of haemodynamic changes after laryngoscopy and tracheal intubation investigate the effect of remifentanil, an opioid with very rapid onset and very short time of action. Remifentanil 1 μg/kg followed by 0.5 μg/kg/min attenuated the pressure response to intubation but was associated with bradycardia and/or hypotension.[28] Other workers found that remifentanil 0.5 μg/kg did not prevent hypertension and tachycardia during rapid sequence induction.[29]

When assessing techniques to ameliorate the cardiovascular responses to intubation, the drugs used to induce anaesthesia may influence these results. We induced anaesthesia with thiopentone which would cause some hypotension and tachycardia. However, before giving thiopentone, we also administered midazolam, fentanyl and a defasciculating dose of vecuronium. It is well known that midazolam or vecuronium does not alter the HR on their own, but fentanyl reduces HR and succinylcholine also produces similar effects, i.e., sinus bradycardia. The tachycardia after thiopentone would have been nullified by the fentanyl- and succinylcholine-induced sinus bradycardia. In our patients, we observed an increase in HR which is attributed solely due to laryngoscopy and intubation only, and gabapentin was found to suppress the increase in HR. We counteracted the fall of blood pressure seen after thiopentone due to peripheral vasodilatation with an infusion of crystalloid solution. None of our patients exhibited hypotension after induction, so the attenuation of hypertensive response seen after gabapentin could be solely due to the gabapentin only as this suppression was not seen after placebo.

Another valuable observation from our study was that patients who were not pre-medicated with gabapentin, i.e.,. the placebo group, showed a statistically significant high values of baseline HR. This shows that gabapentin as a pre-medicant produced stabilization of HR even before any intervention was done.

We pre-medicated our patients with three doses of gabapentin in this study, unlike Fassoulaki et al.[16] who used four doses of gabapentin. Our three doses were administered at 18:00 h, 24:00 h (on the night before surgery) and 06:00 h on the day of surgery. We omitted the 12:00 h (on the day before surgery) dose because of non-availability of theatre lists by this time. Another reason was that we also wanted to see if only three doses of gabapentin are sufficient to produce adequate blood levels which would attenuate the haemodynamic responses. A review of the literature of pharmacology of gabapentin shows that sufficient antiepileptic effect could be achieved even with three doses.[30]

We studied patients up to 65 years only, as elderly patients take more often drugs such as antidepressants, hypnotics and antihypertensives. Sensitivity to drugs and the cardiovascular effects of gabapentin are not studied in them extensively.[31],[32] Aged patients should comprise a different group with doses of gabapentin duly adjusted to age.

Our results showed that gabapentin attenuated the pressor response to tracheal intubation, as systolic, diastolic, MAPs and also HRs were significantly lower in the gabapentin versus control group.

Singhal et al.[33] compared the effects of oral clonidine pre-medication with that of oral gabapetin on haemodynamic responses to laryngoscopy and intubation.[33] They found that oral clonidine 200 μg when given 90 min before anaesthesia provides good attenuation of haemodynamic response to laryngoscopy and intubation as compared with oral gabapentin (900 mg), which also fairly obtunded the hypertensive response but not the tachycardiac response. Clonidine also provided better sedation and anxiolysis when compared with gabapentin. Others have also found similar results of not significant response with regard to HR changes but effective attenuation of blood pressure changes.[34],[35]

In contrast, we found gabapentin effectively attenuated the increase in the HR also. Fassoulaki et al.[16] who used four doses of gabapentin also observed a significant suppression of HR along with SBP, DBP and MAP. This could possibly be due to the adequacy of blood levels of gabapentin with three doses given at regular intervals, as in our study where as a single dose of 900 mg may not attain the required blood levels for controlling the HR. Although only 800 mg of gabapaentin was given orally 2 h prior to the induction, In a study[36] it was that there was a found significant suppression of HR when compared to placebo which was similar to our study results.

The exact mechanism by which gabapentin attenuates the pressor response to laryngoscopy and intubation is unknown. The drug inhibits membrane voltage-gated calcium channels, thus acting in a manner similar to calcium channel blockers.[37] Another explanation for its attenuation of pressor response may be that gabapentin was shown to slightly reduce the release of several monoamine neurotransmitters from mammalian brain tissues in vitro.[38],[39]

Pre-clinical data gathered early in the development of gabapentin showed anxiolytic[40] effects in several animal models. Isolated anecdotal reports emerged over the years and indicated the successful use of gabapentin to treat anxiety symptoms. This may be another explanation for the attenuation of pressor response.

We did not measure stress mediators such as endogenous plasma catecholamines or cortisone. Such measurement of endogenous catecholamines would give useful information. We did not score sedation as scoring sedation before induction of anaesthesia would interfere with the double blinding of the study.

Parenteral preparation (injectable form of gabapentin) is not available at present. Only oral formulations are available which will take in these present dosing schedule many hours to reach adequate plasma concentrations so this drug cannot be used to attenuate the pressor response in emergency cases. However, in a study[17] it was observed that the effects of oral gabapentin given in a dosage of 800 mg 1 h prior to surgery and noticed that gabapentin had attenuated the pressor response to laryngoscopy and intubation after standard elective induction. The effects of oral gabapentin given alone or in combination with dexamethasone, 1 h before the start of surgery also attenuated the pressor response to laryngoscopy and intubation was studied.[18] However, further studies are needed to explore its use in the emergency scenario, particularly administering drugs orally with sips of water in emergency, <2 h prior to induction on a possibly full-stomach patients.

We conclude that gabapentin given as pre-medicantion in three divided doses before surgery attenuated the pressor response to laryngoscopy and intubation (viz., HR, SBP, DBP and MAP in patients undergoing elective non-cardiac surgeries.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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