Introduction

Laryngoscopy and intubation performed as a part of GA is a noxious stimulus and is capable of producing marked circulatory effects known as presssor response characterized by tachycardia, hypertension and altered rhythm^[1],[2]. Various drugs and techniques have been proposed to prevent or attenuate this response such as deepening of anaesthesia^[3],omitting cholinergic premedication^[4], use of vasodilators such as nitroglycerine^[5],beta blockers^[6],calcium channel blockers^[7] and opioids^[8] but no single technique has achieved universal acceptance.

Gabapentin, a structural analogue of γ-animobutyric acid, is used as an anticonvulsant drug. The inhibition of Ca2+ flux in muscle cells with a consequent inhibition of smooth muscle contraction might explain the effectiveness of gabapentin in attenuation of the pressor response to laryngoscopy. Thus it act in a manner similar to Ca2+ channel blocker^[9].

Clonidine is a α₂-adrenoceptor agonist with sedative and analgesic effects, also has beneficial effect of blunting hyperdynamic responses due to laryngoscopy and tracheal intubation as it decreases the release of stress hormones ^[10]. Present study was undertaken to study the effects of clonidine 300µg, gabapentin 800mg and their combination in half doses on attenuation of pressor response to laryngoscopy and intubation.

Materials and methods

After obtaining informed consent and approval from the hospital ethics committee, the randomized controlled trial was conducted on 120 patients of either sex of age between 20-60 years of ASA Grade I and II admitted at least 24 hours before for elective surgery requiring GA. After taking a detailed history, thorough general physical and systemic examination, all pertinent investigations were carried out to exclude any systemic disease. Exclusion criteria for this study were-Anticipated difficult intubation, consumption of antihypertensive drugs, sedatives, hypnotics and antidepressant drugs except those included in the study.

Patients were prepared with 6 hours preoperative fasting. Omeprazole 40mg was given night before surgery to all the patients.

Patients were randomly allocated to one of the following four groups of 30 each according to the drug given as pretreatment 60 min. prior to induction of anaesthesia:-

Group A - received 800mg of gabapentin orally.

Group B - received 300 µg of clonidine orally.

Group C - received 400mg of gabapentin and 150µg of clonidine orally.

Group D - Patients in this group were not given any pretreatment and served as the control group for the study.

Anaesthesia technique

Results

Figure 1

Table 1 Comparison of age and weight in the four groups

On comparing the four groups using ANOVA, the difference among the groups was statistically insignificant (p-value<0.05).

Figure 2

TABLE 2: Heart rate changes in the groups before and after laryngoscopy and intubation

The mean difference is significant at p-value < 0.05 and highly significant at p-value < 0.001.

Figure 3

TABLE 3: Systolic blood pressure changes in the four groups before and after laryngoscopy and intubation

The mean difference is significant at p-value < 0.05 and highly significant at p-value < 0.001.

Figure 4

TABLE 4 : Diastolic blood pressure changes in the four groups before and after laryngoscopy and intubation

The mean difference is significant at p-value < 0.05 and highly significant at p-value < 0.001.

Figure 5

TABLE 5: Mean arterial pressure in the four groups before and after laryngoscopy and intubation

The mean difference is significant at p-value < 0.05 and highly significant at p-value < 0.001.

Figure 6

TABLE 6: Intergroup comparison of heart rate, systolic blood pressure, diastolic blood pressure and mean arterial blood pressure.

The mean difference is significant at p-value < 0.05 and highly significant at p-value < 0.001.

Result Summary

Table 1 shows distribution of mean age and weight in each group with no significant differences between the four groups(respectively; p-value<0.05).

HR: There was statistically significant rise in heart rate after laryngoscopy and intubation at 0 min in all the groups (p<0.05) except in group B. Heart rate decreased to insignificant levels in group A (p-value>0.05) at 3 min., whereas it remained significant in group C and D upto 10 min.

SBP: It was observed that after laryngoscopy and intubation SBP shot up significantly (p-value<0.001) in all the groups except in group A. In group A there was a fall in SBP at 1min. after laryngoscopy and intubation which continued upto the 10 ^th min.

DBP: It was observed that after laryngoscopy and intubation diastolic blood pressure shot up significantly (p-value<0.001) in all the groups except in group A. In group A there was a fall in diastolic blood pressure at 1min. after laryngoscopy and intubation which continued upto the 10 ^th min.

MAP: There was statistically highly significant (p-value>0.01) rise in mean arterial pressure in all the groups except in group A. In group A statistically significant fall in mean arterial pressure was observed 1 min. after laryngoscopy and intubation (p-value<0.001) which continued upto 10min. after laryngoscopy and intubation.

Discussion

All the four groups were comparable in weight and age(table 1).There was no statistically significant difference in HR, SBP,DBP and MAP amongst the four groups before intubation(table2,3,4,5). The statistically significant fall in HR and arterial blood pressure was noted in all the four groups which can be attributed to the use of propofol as induction agent (table2,3,4,5).

In group A, HR, SBP, DBP and MAP were significantly lower in comparision to group D at various time intervals of our study (table 6). Our observations are in accordance with the findings of Kiran and Verma^[11]. Memis et al reported complete attenuation of reflex increase in heart rate and MAP after laryngoscopy and intubation with 800mg of gabapentin when given 1 hour before surgery^[12]. However, another study reported that gabapentin attenuate increase in blood pressure but not the tachycardia response to laryngoscopy and intubation^[13].

In group B, HR was significantly lower in comparison to group D as various time intervals. Though there was an increase in SBP, DBP and MAP, but it was of smaller magnitude and for lesser duration in group B when compared with group D (table 6).Our findings are in accordance with those of Batra et al^[14], Orko et al^[15] and Pouttu^[16]. Wright et al observed attenuation of HR in response to intubation in clonidine pretreated group but the magnitude of increase in arterial pressure was not altered^[17]. In contrast to these findings, Nishikawa et al reported an insignificant rise in SBP and MAP in response to tracheal intubation but the tachycardia response was not attenuated^[18].

In group C the significant increase in HR, SBP, DBP and MAP observed just after intubation which persisted for 5min were comparable with those in group D.

While doing intergroup comparison, we found that there was no statistically significant difference between group A and B with regard to HR at 0 and 1 min. after laryngoscopy and intubation (p-value>0.05) (Table 6). But the mean HR was lesser in group B as compared to group A at 3, 5 and 10 min. after intubation which was statistically significant (p-value<0.05) (Table 6).The statistically significant higher arterial blood pressure was noted in group B as compared to group A at various time intervals of the study (p-value>0.001) (Table 6).The results of our study are in accordance with the findings of Marashi et al^[19]. The reflex increase in HR and arterial blood pressure in group C was statistically significant as compared to groups A and B. Koc et al examined the role of gabapentin 800mg and dexamethasone 8mg and their combination in varicocele surgery^[20]. They showed that combination of both the drugs provides significant decrease in MAP and heart rate values in first 10min. after induction of anaesthesia than the single drug gabapentin or dexamethasone. We did not find any advantage of using combination of gabapentin and clonidine in the half doses over the individual drugs. This may be because we have used their half doses. No cardiac rhythm disturbances were noted in any of the groups

Thus, we conclude that pretreatment with both gabapentin 800mg and clonidine 300µg is effective in attenuation of pressor response to laryngoscopy and intubation. However, the rise in blood pressure is better attenuated by gabapentin. Though clonidine abolishes increase in heart rate after intubation more effectively but the difference was not statistically significant when compared to gabapentin upto 1min. The combination of these two drugs in the studied dosage was not effective in controlling the HR and blood pressure in response to direct laryngoscopy and intubation.

Acknowledgment

We would like to extend our sincere thanks to Dr Dinesh Kumar, Assist. Professor, Deptt of community medicine, government medical college Jammu, for his immense help in the interpretation and analysis of statistical data concerning the study.