TITLE: Comparative Study of Oral Gabapentin, Pregabalin, and Clonidine as Premedication for Anxiolysis, Sedation, and Attenuation of Pressor Response to Endotracheal Intubation

  ABSTRACT.INTRODUCTION:
The aim of the present study was to evaluate and compare the effect of clonidine 200 μg and gabapentin 900 mg and pregabalin 150 mg in attenuation of the hemodynamic response to laryngoscopy and intubation in normotensive patients undergoing elective surgery.

ABSTRACT.METHODS:
Ninety adult patients between 18 and 60 years are enrolled in the study. Patients with American Society of Anesthesiologists Grade-I and Grade-II are included which are posted for elective surgery under general anesthesia. Patients were divided into three groups: A, B, and C and received oral drugs 90 min before induction of general anesthesia, pregabalin 150, gabapentin 900mg, and clonidine 200 μg, respectively. Hemodynamic parameters such as heart rate and blood pressure were noted just before the (basal) administration of the drug, and in operation room, readings were recorded before intubation (T0) and after intubation at 1, 3, 5, and 10 min. Sedation and anxiety score were noted after 1 h of oral administration of the drug.

ABSTRACT.RESULTS:
Mean arterial pressure was well attenuated by pregabalin than others, and mean heart rate following laryngoscopy and intubation was attenuated by clonidine group significantly.

ABSTRACT.CONCLUSION:
We conclude that oral pregabalin and gabapentin attenuate blood pressure response fairly well and heart rate significantly attenuated by clonidine. All three drugs are very effective for relieving anxiety and improving sedation.

BODY.I:
Laryngoscopy and intubation have detrimental effect on the cardiovascular system. This effect is more exaggerated when the patient has already preexisting diseases mainly coronary artery diseases, myocardial infarction, and intracranial aneurysm. Hence, to decrease this adverse effect of laryngoscopy and intubation, a number of drugs are used such as b-blockers, lignocaine, and opioids. In this study, we are going to study the effect of oral gabapentin, pregabalin, and clonidine for attenuation of the hemodynamic response due to laryngoscopy and intubation.  Gabapentin is structurally related to neurotransmitter gamma-aminobutyric acid. It is used for controlling seizers and controlling neuropathic pain, restless leg syndrome.  Clonidine is α2-adrenergic agonist. It is used in anesthesia for sedation, anxiolysis, and as adjuvant for regional blocks. It helps in attenuation of hemodynamic effect by blocking the central sympathetic outflow.  Pregabalin binds to same receptors as gabapentin and has a similar pharmacological profile. It is used for sedation, and anxiolysis is anesthesia.  The aim of the present study was to evaluate and compare the effect of clonidine and gabapentin and pregabalin in obtunding hemodynamic response to laryngoscopy and intubation in normotensive patients undergoing elective surgery.

BODY.M:
The study was approved by Hospital Ethical Committee, and informed consent from all the participants was obtained. Ninety adult patients between 18 and 60 years are enrolled in the study. Patients with American Society of Anesthesiologists (ASA) Grade-I and Grade-II are included which are posted for elective surgery under general anesthesia. Patients with ASA Grade III and IV, difficult intubation are excluded from the study.

BODY.M.STUDY DESIGN:
It was a prospective, randomized, and double-blind study. Randomization was performed by envelope method. All patients had undergone preanesthetic examination for detailed history, examination, and appropriate investigations. Patients were randomly allocated to three groups of thirty each. Each group received oral drugs 90 min before surgery with sip of water. Group A patients received pregabalin 150mg, Group B patients received gabapentin 900mg and Group C clonidine 200 μg. Pulse oximetry, noninvasive arterial blood pressure, electrocardiogram were the standard monitoring used in the operating room. Intravenous line is taken, and after preoxygenation for 3–5 min, propofol 2 mg/kg was used as induction agent followed by succinylcholine 2 mg/kg. Patient is manually ventilated, after that, laryngoscopy and intubation were performed by trained anesthetics. The patient is maintained with oxygen, nitrous oxide, isoflurane, and atracurium thereafter. Sedation score and anxiety score were noted in preanesthetic room.

BODY.M.ANXIETY SCORE:

0: Patient quiet and comfortable1: Patient uneasy2: Patient worried or anxious3: Patient very worried or very upset.


BODY.M.SEDATION SCORE:

1: Wide awake2: Sleeping comfortably but responding to verbal commands3: Deep sleep but arousable4: Deep sleep but not arousable.
  Hemodynamic parameters such as heart rate and blood pressure were noted just before the (basal) administration of drug, and in operation room, readings were recorded before intubation (T0) and after intubation at 1, 3, 5, and 10 min.  Patients were monitored for any side effects pertaining to drugs. Quantitative data for intragroup comparison were analyzed by using independent t-test. Intergroup comparisons were done by one-way ANOVA test. Chi-square test was used for categorical data (age, gender, ASA grade). P < 0.05 was considered statistically significant.

BODY.R:
In our study, the demographic data with respect to age, sex, and ASA grade were statistically comparable in the three groups.  The mean heart rate [Table 1] following laryngoscopy and intubation among the groups receiving clonidine was lesser than the group receiving pregabalin and gabapentin and was statistically significant (P < 0.05) at 5 min and 10 min.   Table 1 Heart rate   Whereas the mean blood pressure [Table 2] was significantly less among the patient group receiving pregabalin following laryngoscopy and tracheal intubation than other groups during 1 min and 3 min.  Table 2 Mean arterial pressure   The difference of sedation and anxiety score was statistically significant in all the groups. And it is highly statistically significant in pregabalin group [Tables 3 and 4].  Table 3 Anxiety score   Table 4 Sedation score 

BODY.D:
In this study, all groups are similar to baseline hemodynamic parameters [Tables 1 and 2].  Namratha et al.[1] compared gabapentin and pregabalin in dose of 800mg and 150mg respectively as premedication for attenuation of pressure response. Their findings were similar to our study showing pregabalin more effective than gabapentin both for heart rate and mean arterial pressure response.  de-Paris et al.[2] and Kiskira et al.[3] both found in their studies that gabapentin effectively decreases the anxiety. This is in accordance with our study [Table 3].  Similarly, Anju et al.[4] done study comparing pregabalin 300mg and gabapentin 900 mg for relieving preoperative anxiety and sedation. They concluded that both significantly reduces anxiety and sedation. As shown in Table 4, we found that all three drugs significantly reduces anxiety and sedation, maximally by pregabalin.  Gupta et al.[5] also stated in their study that oral pregabalin 150 mg effectively attenuates hemodynamic response to laryngoscopy and intubation. They had given drug 60–75 min before surgery.  Memis et al.[6] studied two doses of oral gabapentin 800 mg and 400 mg. And found that group receiving 800 mg had significant reduction in pressor response due to laryngoscopy and intubation.  Rastogi et al.[7] also stated in their study that oral 150 mg of pregabalin significantly attenuate hemodynamic response to orotracheal intubation.  Archana et al.[8] studied effect of 150 mg oral pregabalin and 200 μg oral clonidine for attenuation of orotracheal response. And found that pregabalin significantly reduces the response more than clonidine group. We also found similar result in our study.  Marashi et al.[9] 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 found that gabapentin attenuates the response better than clonidine. However, lowest heart rate reported in the study was in clonidine group at 10 min. We also reported lowest heart rate in clonidine group but at 5, 10 min.  Gupta et al.,[5] Memis et al.,[6] Archana et al.[8] did not found any significant side effects related to drugs, similar to our study.  Our study shows similar results as Nanda et al.,[10] they studied oral clonidine 0.2 mg and 900 mg gabapentin for similar comparison. They also found gabapentin better than clonidine.  Similarly, Montazeri et al.[11] found gabapentin to be better than clonidine for attenuation of pressure response.

BODY.C:
We conclude that for attenuation of pressure response for orotracheal intubation, pregabalin is fairly better than gabapentin and clonidine. Moreover, clonidine is better for attenuation of tachycardia response.  All three drugs provide better sedation and anxiolysis if given orally before operation.

BODY.C.FINANCIAL SUPPORT AND SPONSORSHIP:
Nil.

BODY.C.CONFLICTS OF INTEREST:
There are no conflicts of interest.

Question: Compared to clonidine 200 μg, gabapentin 900mg what was the result of pregabalin 150 on the mean blood pressure?
Evidence: The mean heart rate [Table 1] following laryngoscopy and intubation among the groups receiving clonidine was lesser than the group receiving pregabalin and gabapentin and was statistically significant (P < 0.05) at 5 min and 10 min.
Answer: significantly decreased