European Journal of Cardiovascular Medicine

Laryngoscopy and endotracheal intubation are potent stimuli that can induce increased sympathetic activity leading to tachycardia, hypertension and dysrhythmias. It may have deleterious respiratory, neurological and cardiovascular effects.^(1,2)The ideal premedicant should be effective and pleasant to be taken orally, have analgesic and non emetic properties, should not impair cardiovascular stability or depress respiration, should have antisialagogue effect and should effectively alleviate apprehension of the patient.⁽³⁾Laryngoscopy and intubation are associated with cardiovascular changes such as hypertension, tachycardia, dysrhythmias and even, myocardial ischaemia⁽⁴⁾ and increased circulating catecholamines.⁽⁵⁾

To attenuate the hemodynamic response, many techniques have been tried but none ideal. Still there is search for newer drugs to attenuate the pressure response. Gabapentin is a relatively new drug, which was introduced as antiepileptic but proved to be effective in controlling neuropathic pain^.(6). Alpha-2 adrenoceptor agonists have been used as premedicants because of their beneficial properties in anaesthesia. The only clinically available alpha-2 adrenergic agonist in our country is clonidine, which is mainly used as an anti hypertensive agent, but has many properties of ideal premedicant and also has beneficial effects on haemodynamics during stressful conditions like laryngoscopy and endotracheal intubation^(7,8).

We conducted this randomized double blind clinical trial study to compare haemodynamic responses of laryngoscopy and tracheal intubation using 900 mg gabapentin and 0.3 mg clonidine that was administered 90 minutes prior to surgery as a premedicant.

Following the approval by the Institutional Ethical Committee, a hospital based prospective double blinded study was undertaken among 70 adult patients who presented for elective surgery under general anesthesia. Informed consent was obtained to participate in the study. Random allocation of patients into two groups of 35 patients each group C (N=35) and group G (N=35) was done using shuffled closed opaque envelope technique. A day prior to surgery pre-operative evaluation of patients was done, a detailed medical history and a through clinical examination including assessment of airway was conducted. All the subjects were given Ranitidine 150 mg orally, on the night before surgery and were kept nil per oral 6 hours for solids and 4 hours for clear fluids. Group C patients were given clonidine (0.3 mg) orally 90 minutes prior to surgery. Group G patients received gabapentin (900 mg) orally 90 minutes prior to surgery. On arrival to the operation theater, IV access using 18G cannula on the nondominanth and was secured. Infusion of Ringer Lactate 500 ml was started 30 minutes prior to induction. All the subjects were connected with the multipara monitor for recording SpO2, Non Invasive Blood pressure (NIBP) and heart rate (HR). Subjects were premedicated with inj. fentanyl 1 to 2 µg per kg. Preoxygenation was done with 100% O2 for 3 minutes. General anaesthesia was induced with Inj. propofol 1 to 2mg/kg I.V slowly and the end point for induction was taken as loss of eye lash reflex. Inj. Vecuronium 0.1mg/kg I.V was given and subjects were mask ventilated for 3 minutes. All the subjects were intubated with appropriate size cuffed ET tube with gentle laryngoscopy and tracheal position of the tube confirmed by end tidal carbon dioxide (EtCO2). Anesthesia was maintained with Oxygen+ Nitrous oxide + Inj.Vecuronium + 1-1.5%Isoflurane. In all cases, intubation was done by experienced anaesthesiologist. Hemodynamic response was observed and noted at following timeinstance:T1: at 1st min after intubation,T3: at 3rd min post-intubation,T5: at 5th min post-intubation,T10: at 10th min post-intubation and T15: at 15th min post-intubation. Any untoward complications such as hypotension and bradycardia during induction were noted.

Table 1- Demography of the patients

Table 1 shows demographic data of the two groups and it was comparable.

Table 2- Systolic blood pressure changes

Group G had a significant rise of systolic blood pressure at 1 min following laryngoscopy and intubation, and thereafter it decreased below base line during 3^rd min. However, it returned to  baseline at 5^th minute and thereafter there was a mild increase at the end of 10^th and 15^thminute respectively but was insignificant with respect to baseline. In group C, there was  mild increase in systolic blood pressure during, and 1 min after laryngoscopy and intubation and showed similar  response as that in group G. There was significant difference between the two groups (P <  0.05) at 3^rd, 5^th and 10^th minute respectively. Group G more effectively controlled the surge  associated with laryngoscopy and intubation than group C.

Table 3- Diastolic blood pressure changes

Regarding DBP, group G showed increase in DBP during 1^st min following laryngoscopy and intubation  thereafter it decreases at 3^rd min. And then it returned to baseline values at 5^thmin and increased to 2.4% and 2.6% at the end of 10^th and 15^th min  respectively. In group C, there was mild increase in DBP during 1^st min after laryngoscopy and intubation which  is statistically insignificant. And then it returned to baseline values at 3^rd min and thereafter  it increased to 2.8%, 3.7% and 4.2% at the end of 5^th,10^th and 15^th min respectively. There  was no significance found regarding the change in the values of DBP with respect to both  the groups but group G maintained hemodynamic more steadily than group C.

Table 4- Mean arterial pressure changes

In comparison of MAP, group G and group C showed a significant increase of 4.2% and  2.01% respectively in MAP during 1^st min following laryngoscopy and intubation. Thereafter in group G, it  decreases towards base line following 5^th and 10^th min. In group C, after a mild increase at 1^st min it returned to basal values at 3^rd min and rose to 3.5% and 3.6% to that of basal  values at 10^th and 15^th min. respectively. There was statistically significant difference found  between the two groups at 1^st and 3^rd min only. Though MAP values in group C returned to  basal values at 3^rd min only as compared to 5^th minute in group G, hemodynamics was  maintained better in group G than group C.

Table 5- Heart rate changes

In our study, base line heart rate was comparable between the groups. Heart rate in Group G showed less increase at 1st min after laryngoscopy & intubation and was found to be significant(p<0.05). Both the groups at 10th min showed increase in heart rate from basal values by 8.1% and2.6% in group C and group G respectively. While at 15th min, group C and group G showed increase in heart rate from basal values by 5.4% and 3.0%. Though no significant difference was observed between the groups, hemodynamics was maintained better ingroup G.

Clonidine is a α2 adrenergic agonist, stimulates α2A subtype of α2 adrenergic receptors in the brainstem resulting in a reduction in sympathetic outflow from central nervous system thus causing lowering of arterial pressure by an effect on both cardiac output and peripheral resistance. By its central sympatholytic action, it tends to attenuate the hemodynamic response to any surgical nociceptive stimulus and to improve overall perianesthetic cardiovascular stability.⁽³⁾

Gabapentin which is a structural analogue of the neurotransmitter gamma-aminobutyric acid (GABA) is being used as an anticonvulsant drug is also effective in controlling neuropathic pain. It acts by selective activation of heterodimeric GABA_B receptors. Gabapentin has been used in randomized controlled trials to treat acute post-operative pain and to reduce post-operative opioid requirements.⁽⁹⁾The mechanism by which gabapentin attenuates the pressor response to laryngoscopy andintubation is unknown, the drug inhibits membrane voltage-gated calcium channels, thus acting in the manner similar to calcium channel blockers.⁽⁶⁾

We observed that the difference in raise in SBP was lesser in group G as compared to group C at it was significant(p<0.05) at 3rd,5th and 10th minute. The MAP was also lesser in group G than group C and was significant(p,0.05) at 3rd minute. Heart rate increase was lesser in group G than group C and was significant at the first minute.(p<0.005)

The results of our study are in agreement with the results of studies by Ghignone et al.⁽⁷⁾and Ravalet al⁽¹⁰⁾.The attenuating effect of clonidine on hemodynamic responses to airway manipulation has previously been documented by many studies. Raval DL et al.⁽¹⁰⁾observed reductions in SBP and DBP following premedication with oral clonidine 0.2 mg by 7.63%. In post intubation period, SBP and DBP remained below baseline value producing significant attenuation of rise in SBP due to laryngoscopy and intubation. These findings contrast the findings of the present study as we recorded the mild increase in SBP values by 1.8% and DBP by 2.3% post-intubation in clonidine group. However, DBP values in group C returned to baseline values at 3rd min post-intubation and thereafter it increased to 2.8%, 3.7% and 4.2% at the end of 5th, 10th and 15th min respectively. There was no significance (p>0.05) found regarding the change in the values of DBP with respect to both the groups but group G maintained hemodynamic more steadily than group C. Marashi etal.⁽¹¹⁾studied the comparison of oral gabapentin 900 mg and oral clonidine 0.2 mg, 120 min before surgery for attenuation of the pressor response to orotracheal intubation. They also found that gabapentin attenuates the response better than clonidine. However, lowest heartrate reported in their study was in clonidine group at 10 min. We reported highest heart rate in clonidine group at 5th and 10th min. In clonidine group, the heart rate was higher than baseline at all-time intervals. For instance, there was an increase in heart rate from basal values by 8.1% and 2.6% in group C and group G respectively at 10th min while at 15th min,group C and group G showed increase in heart rate from basal values by 5.4% and 3.0%.Though no significant difference was observed between the groups, clonidine group showed rise in heart rate compared to gabapentin group. Hence, Gabapentin showed to attenuate the heart rate response to laryngoscopy and intubation indicating that it maintains the heart rate closer to baseline than clonidine group. The differences in heart rate in comparison to the other studies might be due to the type of inhalational agent used and its concentration variation. Our study shows similar results as that of Nanda et al.⁽¹²⁾who studied oral clonidine 0.2 mg and 900 mg gabapentin for similar comparison. They also found gabapentin was better than clonidine. Similarly, Montazeri et al.⁽¹³⁾also found gabapentin to be better than clonidine for attenuation of pressure response.

To summarise, when we compared the effects of oral clonidine and gabapentin premedication for attenuation of pressor response to laryngoscopy and intubation, we found almost comparable efficacy of oral clonidine and gabapentin in attenuating pressor response to laryngoscopy and intubation, but more so with gabapentin. In the present study, gabapentin, which was used in a dose of 900 mg and 90 minutes prior to surgery, was found to attenuate the rise in SBP, DBP and MAP at 5, 10 and 15 minutes after intubation. This correlates with the studies done by Fassoulaki et al.⁽⁶⁾and Memis et al.⁽¹⁴⁾Regarding group G, we have seen hemodynamic response was attenuated after 5 min following laryngoscopy and intubation while in the study by Kumari et al.⁽¹⁵⁾who conducted a randomized double blind placebo controlled study of oral gabapentin (900 mg) given 2 h before induction concluded that attenuation of blood pressure response to laryngoscopy and intubation was effectively seen only after 10 min of intubation.

Both oral clonidine (0.3 mg) and oral gabapentin (900 mg) given 90 minutes prior to laryngoscopy are safe and effective prophylactic measures for attenuating hemodynamic response to laryngoscopy and tracheal intubation. But, oral gabapentin (900 mg) is better as compared to oral clonidine (0.3 mg) premedication, in attenuating the hemodynamic response to laryngoscopy and intubation.

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