Comparative Evaluation of the Effects of Pregabalin, Dexmedetomidine, and Their Combination on the Hemodynamic Response and Anesthetic Requirements in Patients undergoing Laparoscopic Cholecystectomy: A Randomized Double-Blind Prospective Study.

BACKGROUND: In this study, we evaluated the efficacy of premedication with dexmedetomidine, pregabalin, and dexmedetomidine-pregabalin combination for attenuating the haemodynamic stress response to laryngoscopy and intubation and pneumoperitoneum (primary outcome), and for reducing anaesthetic requirement (secondary outcome) in patients undergoing laparoscopic cholecystectomy.
METHODS: Ninety ASA physical status classes I-II patients, between 18 to 65 years of age, of either sex, scheduled to undergo laparoscopic cholecystectomy were included in this randomised double blind study. Morbidly obese patients and those with history of hypertension, cardiac, renal, hepatic, endocrine or pulmonary dysfunction were excluded. Patients were randomized to three groups - Group P- received oral pregabalin (150 mg) one hour before induction and 100 mL of i.v normal saline (0.9%) over 10 minutes, 10 minutes before induction; Group D- received i.v dexmedetomidine (1 μg.kg-1) prepared in 100 mL of 0.9% normal saline and given over 10 minutes, 10 minutes before induction, and an oral placebo tablet one hour before induction; and Group C-received a combination of oral pregabalin 75 mg one hour before induction, and IV dexmedetomidine (0.5 μg.kg-1) prepared in 100 mL of 0.9% normal saline over 10 minutes, 10 minutes before induction.
RESULTS: Dexmedetomidine significantly attenuated the stress response to laryngoscopy and intubation and pneumoperitoneum and reduced anaesthetic requirement as compared to the other two groups. Dexmedetomidine was associated with significantly lower mean arterial pressures and higher sedation score in the preoperative and postoperative period and significantly lower heart rate and arterial pressures and reduced anaesthetic requirement in the intraoperative period as compared to the other groups.
CONCLUSION: Dexmedetomidine is a valuable adjunct to the technique of balanced anaesthesia for maintaining haemodynamic stability. Copyright:

INTRODUCTION

Laparoscopy was earlier used mainly for gynecologic procedures. Its extension to gastrointestinal surgical procedures has created new interest and considerations in anesthetic management.

Peritoneal insufflation of CO2 and creation of pneumoperitoneum during laparoscopy induces hemodynamic and ventilatory changes which may complicate anesthetic management. Elevation of the diaphragm due to pneumoperitoneum results in mismatch of pulmonary ventilation and perfusion. These changes result in an increased arterial pressure, increase in systemic vascular resistance, and decrease in cardiac output.[1] In addition, laparoscopic cholecystectomy is performed in reverse Trendelenburg position, which causes diminished venous return, causing a further fall in cardiac output.[1]

General anesthesia with endotracheal intubation and controlled ventilation is the safest and most commonly used technique for laparoscopic procedures. Various analgesic drugs have been used for intraoperative analgesia and for maintaining hemodynamic stability during pneumoperitoneum. α2-agonists are currently used widely as anesthetic adjuvants and analgesics. Dexmedetomidine is a newer α2-agonist with a 1600-fold greater selectivity for α2 as compared to α1 receptors. It possesses hypnotic, sedative, anxiolytic, sympatholytic, and analgesic properties.[2] By reducing the release of norepinephrine (NE), it causes a decrease in mean arterial pressure (MAP) and heart rate (HR). Dexmedetomidine given intravenously before induction of anesthesia attenuates the hemodynamic stress response to laryngoscopy and intubation.[2] It also provides improved hemodynamic stability during the intraoperative period and reduces requirement of analgesics.

More recently, antiepileptic drugs have been used to reduce intraoperative opioid requirement and postoperative pain. Pregabalin, whose structure is similar to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), possesses analgesic and anxiolytic activities and is effective in alleviating the neuropathic component of acute nociceptive pain of surgery. It has also been used as premedication to attenuate the hemodynamic stress response to laryngoscopy and intubation and to decrease intraoperative anesthetic requirement.[3]

In this randomized, double-blind clinical study, we evaluated the efficacy of premedication with dexmedetomidine, pregabalin, and dexmedetomidine-pregabalin combination for attenuating the hemodynamic stress response to laryngoscopy and intubation and pneumoperitoneum (primary outcome), and for reducing anesthetic requirement (secondary outcome) in patients undergoing laparoscopic cholecystectomy.

MATERIALS AND METHODS

The study was conducted after obtaining written informed consent from patients and after being duly approved by the Institute Ethics Committee of Vardhman Mahavir Medical College and Safdarjung Hospital. Ninety American Society of Anesthesiologists Physical Status Classes I and II patients, between 18 and 65 years of age, of either sex, and posted for laparoscopic cholecystectomy were included in this double-blind study. Morbidly obese patients and those with a history of hypertension and cardiac, renal, hepatic, endocrine or pulmonary dysfunction were excluded from the study. All patients received oral alprazolam 0.5 mg and ranitidine 150 mg, the night before surgery. In the preoperative room, an intravenous (IV) line with an 18G cannula was secured. Preoperative vital parameters such as HR, MAP, oxygen saturation (SpO2), and electrocardiogram (ECG) were recorded.

Patients were randomized to one of three groups –Group P – Pregabalin group was given oral pregabalin (150 mg) 1 h before induction and 100 mL of IV normal saline (0.9%) over 10 min, 10 min before induction; Group D – Dexmedetomidine group was given IV dexmedetomidine (1 μg/kg) prepared in 100 mL of 0.9% normal saline and given over 10 min, 10 min before induction, and an oral placebo tablet 1 h before induction; and Group C – Combination group was given a combination of oral pregabalin 75 mg 1 h before induction and IV dexmedetomidine (0.5 μg/kg) prepared in 100 mL of 0.9% normal saline over 10 min, 10 min before induction. Randomization was done by the second author using computer-generated random numbers which were contained in a sealed envelope. This was handed over to another anesthesiologist who prepared the appropriate drugs. Premedication (oral and IV) was administered by the first author who remained blinded to its contents. Patient assessment and observations were recorded by the blinded researcher in the preoperative room, operation theater, and in the recovery room. HR, noninvasive blood pressure (NIBP), SpO2, and Ramsay's sedation scale (ranging from 1-anxious/agitated to 5-no response) were monitored at 10, 20, 30, 40, 45, 50, 55, and 60 min after premedication (PT10, PT20, PT30, PT40, PT45, PT50, PT55, and PT60, respectively).

On arrival in the operation theater, routine monitoring with ECG, pulse oximetry, and NIBP was started. Patients were induced with fentanyl 1.5 μg/kg and propofol (till loss of verbal response), followed by vecuronium 0.1 mg/kg. Following this, invasive positive-pressure ventilation was instituted with O2, N2O, and isoflurane. Laryngoscopy was done 3 min after administration of relaxant, and an appropriate-sized endotracheal tube was inserted by an experienced anesthesiologist. A nasogastric tube was inserted orally to deflate the stomach. Patients were maintained on O2, N2O, and isoflurane with intermittent boluses of vecuronium as required. After cleaning and draping, CO2 insufflation was started at 2 L/min to create a pneumoperitoneum, and thereafter, intra-abdominal pressure was maintained at 12 mmHg. Fluid requirement was calculated as per fluid deficit, maintenance and third space losses, and Ringer's lactate was administered. Ondansetron (0.1 mg/kg) and diclofenac 75 mg IV were given half an hour prior to the end of surgery. After surgery, local infiltration of the incision ports was carried out with 0.25% bupivacaine. Neostigmine 0.05 mg/kg and glycopyrrolate 0.01 mg/kg were given for reversing residual neuromuscular blockade, and after adequate reversal, patients were extubated.

In the intraoperative period, time required for laryngoscopy and intubation (defined as the time from introduction of the laryngoscope till the confirmation of endotracheal tube placement by end-tidal CO2) and duration of pneumoperitoneum and surgery were noted. Hemodynamic parameters were monitored before induction (IT0), after 1, 2, and 3 min of induction (IT1, IT2, IT3), after 1, 3, 5 and 10 min of intubation (IT4, IT5, IT6, IT7), every 15 min subsequently (IT11, IT12, and so on), before and after creation of pneumoperitoneum (IT8 and IT9), and at the end of pneumoperitoneum (IT10). Hemodynamic parameters were maintained within 20% of baseline values. To achieve this, isoflurane concentration was increased in increments of 0.2% (till a maximum of 1%) and fentanyl was administered in increments of 0.5 μg/kg when isoflurane requirement rose above 1%. The average isoflurane dial concentration at specified time intervals was noted. Total average isoflurane dial concentration was calculated by multiplying the dial concentration with the time (minutes) for which that concentration was maintained and divided by the total duration of surgery.

Postoperatively, time taken for tracheal extubation and to respond to verbal commands after giving reversal was noted. Hemodynamic parameters, postoperative pain (assessed using Visual Analog Scale [VAS]), and sedation (assessed using Ramsay's sedation scale) were noted at 15 min, 1 h, and 2 h after reversal (PoT15, PoT60, and PoT120).

Taking our primary outcome as attenuation of hemodynamic stress response to laryngoscopy and intubation and to pneumoperitoneum and assuming the minimum difference in MAP as 15% between any two groups (Group P, Group D) and Group C, with an α error – 0.05 and β error – 20 and power of the study as 80%, the minimum sample size was calculated to be 30 patients in each group. Data have been presented as mean for quantitative variables (age, weight, MAP, and HR) and percentage for categorical variables. Statistical significance for quantitative variables has been carried out by ANOVA test/nonparametric Kruskal–Wallis test and for categorical variables by Chi-square/Fisher's exact test. The level of statistical significance has been set as P ≤ 0.05. Data were analyzed using SPSS Statistical Software version 16.0 (IBM, New Delhi, India).

RESULTS

The demographic profile of patients and mean duration of pneumoperitoneum and surgery were comparable among the three groups [Table 1].

Table 1

Demographic characteristics, duration of surgery, and pneumoperitoneum

	Group D Dexmedetomidine	Group P Pregabalin	Group C Combination	P
Age (years)	37.067±11.6942	33.133±10.6698	36.133±11.982	0.385
Height (cm)	160.433	158.4	159.033	0.355
Weight (kg)	61.5333	54.9	58.133	0.066
Duration of surgery (min)	56.5	58.1667	58.5	P versus D - 0.938P versus C - 0.911D versus C - 0.997
Duration of pneumoperitoneum (min)	46.6667	47.5	48	P versus D - 0.983P versus C - 0.957D versus C - 0.994

Group P=Pregabalin group, Group D=Dexmedetomidine group, Group C=Combination group

In the preoperative period, analysis of HR showed a significant reduction at 20, 15, 10, and 5 min and just before induction (P = 0.000–0.011) in Group D, at all preoperative time intervals (P = 0.000–0.014) in Group P and at 40, 15, 10, and 5 min and just before induction (P = 0.000–0.041) in Group C, as compared to the baseline. However, there was no significant difference in mean HR among the three groups in the preoperative period.

A significant reduction in MAP was observed from 15 to 20 min till just before induction in all the three groups (Group D – P = 0.000–0.030, Group P – P = 0.006–0.049, and Group C – P = 0.000–0.005). On comparing the groups, we found that mean MAP was significantly lower in Group D as compared to Group P (P = 0.000–0.002) and Group C (P = 0.033–0.042) from 5 to 10 min before induction, till the start of induction.

In the intraoperative period, a significant reduction in mean HR was noted in all the three groups at induction (P = 0.000), and this lasted till 3 min after induction (P = 0.000). In contrast to Groups P and C, in which there was a significant increase (Group P – P = 0.000–0.001, Group C – P = 0.000–0.003), Group D was associated with a significant decrease in HR starting from just after laryngoscopy and intubation till 75 min later and including before, after, and at the end of pneumoperitoneum (P = 0.000–0.027) as compared to the baseline.

Mean HR was significantly lower in Group D as compared to Group P at 3,10, 30, 45, 60, and 75 min after intubation (P = 0.001–0.045) and after creation of pneumoperitoneum (P = 0.049). Mean HR was significantly lower in Group D as compared to Group C at 30, 45, 60, and 75 min after intubation (P = 0.009–0.047) [Figure 1].

Figure 1

Changes in intraoperative heart rate. IT 0 – At the time of induction, IT2 – 2 min after induction, IT4 – 1 min after intubation, IT6 – 5 min after intubation, IT8 – Before creation of pneumoperitoneum, IT11 – 15 min after intubation, IT13 – 45 min after intubation, IT15 – 75 min after intubation

A significant reduction in MAP was observed in Group D at induction, at 1, 2, and 3 min after induction (P = 0.000), at 1, 3, 5, and 10 min after laryngoscopy and intubation (P = 0.000–0.001), and before the creation of pneumoperitoneum (P = 0.001), as compared to the baseline. Groups P and C were associated with a significant reduction in MAP till 3 min after induction (Group P – P = 0.008–0.022 and Group C – P = 0.000), but a significant increase in MAP was observed after laryngoscopy and intubation, and after the creation and end of pneumoperitoneum and throughout the period of surgery (Group P – P = 0.000–0.015 and Group C – P = 0.000–0.008) as compared to the baseline.

Mean MAP was observed to be significantly lower in Group D as compared to Groups P and C after laryngoscopy and intubation, before, after, and at the end of pneumoperitoneum and at all intraoperative time intervals (Group D vs. Group P – P = 0.000–0.037 and Group D vs. Group C – P = 0.000–0.024). There was no difference in mean MAP between Groups P and C in the intraoperative period [Figure 2].

Figure 2

Preoperative, intraoperative, and postoperative changes in mean arterial pressure. PT20 – 40 min before induction, PT40 – 20 min before induction, PT50 – 10 min before induction, PT60 – Just before induction, IT0 – Time of induction, IT4 – 1 min after intubation, IT11 – 15 min after intubation, IT12 – 30 min after intubation,IT13 – 45 min after intubation,IT14 – 60 min after intubation, IT 15 – 75 min after intubation, PoT 15 – 15 min after extubation, PoT 60 – 60 min after extubation, PoT 120- 120 min after extubation

A significant reduction in postoperative HR was observed in Group D at 15, 60, and 120 min after extubation (P = 0.000) and a significant increase was observed in Groups P and C after extubation and at 15 min after extubation (P = 0.000) as compared to the baseline. There was no significant difference in mean HR among the three groups in the postoperative period.

There was a significant increase in MAP in all the groups after extubation (Group D – P = 0.015, Group P – P = 0.000, and Group C – P = 0.000) as compared to the baseline. Whereas, in Group D, there was a significant reduction in MAP at 60 and 120 min after extubation (P = 0.028 and 0.001, respectively), in Groups P and C, there was a significant rise at 15 and 60 min, respectively (Group P – P = 0.000–0.045 and Group C – P = 0.000). Mean MAP was significantly lower in Group D as compared to Groups P and C (Group D vs. Group P – P = 0.000–0.002 and Group D vs. Group C – P = 0.000–0.001) at all postoperative time intervals. There was no difference in mean MAP between Groups P and C postoperatively.

A significant reduction in the total average isoflurane dial concentration was observed in Group D as compared to Groups P and C (P = 0.001). The average isoflurane dial concentration was found to be significantly lower in Group D as compared to Groups P and C after laryngoscopy and intubation (P = 0.000), before, after, and at the end of pneumoperitoneum (P = 0.000) and throughout the period of surgery (P = 0.000–0.002). There was no significant difference in the total average isoflurane dial concentration between Groups P and C. Dose of propofol needed for induction was found to be significantly reduced in Group D as compared to Groups C and P (Group D vs. Group P – P = 0.000, Group D vs. Group C – P = 0.000) and in Group C as compared to Group P (P = 0.000) [Figure 3].

Figure 3

Anesthetic requirement of propofol and isoflurane

43.33% of patients in Group P, 26.66% in Group C, and 10% in Group D required an additional dose of fentanyl. There was a significant difference in additional fentanyl requirement between Group D and Group P (P = 0.00741). There was no significant difference in additional fentanyl requirement between Groups D and C (P = 0.180580) and Groups C and P (P = 0.278912), respectively.

The average time taken for extubation and to respond to verbal commands after giving reversal was significantly longer in Groups D and C as compared to Group P (Group D vs. Group P – P = 0.000; Group C vs. Group P – P = 0.000) [Table 2].

Table 2

Time taken for extubation and to respond to verbal commands

Groups	Time taken for extubation (s)	Time taken to respond to verbal commands (s)
Group D (dexmedetomidine)	192.6667	287.3333
Group P (pregabalin)	136	190.3333
Group C (combination)	182	270.3333

Group D versus Group P=P: 0.000, Group C versus Group P=P: 0.000

In the preoperative period, Groups D and C showed a significant increase in the sedation score from 5 min before induction (P = 0.000) till just before induction (P = 0.000). On comparing the groups, we found that mean sedation score in Groups D and C was significantly higher than Group P at 5 min before induction (P = 0.000) and just before induction (P = 0.000) and mean sedation score in Group D was significantly higher than Group C just before induction (P = 0.020).

Mean sedation score was significantly higher in all the groups at 15 min and 60 min after extubation as compared to the baseline (P = 0.000). Mean sedation score was higher in Group D as compared to Groups P and Group C (P < 0.05) at 15 min and 60 min after extubation. There was no significant difference in the mean sedation score among the three groups at 120 min after extubation [Table 3].

Table 3

Pre- and postoperative mean Ramsay Sedation Score

Time	Group D (dexmedetomidine)	Group P (pregabalin)	Group C (combination)
PT0-1 h before induction (baseline)	1.933	1.9	1.933
PT20-40 min before induction	1.933	1.933	1.933
PT40-20 min before induction	1.933	1.9	1.933
PT50-10 min before induction	1.933	1.9	1.933
PT55-5 min before induction	3.167α,β	1.9ε	2.867α
PT60 - just before induction	3.667α,β,δ	1.9ε	3.167α
PoT15-15 min after extubation	3.4α,β,δ	2.933α	2.833α
PoT60-60 min after extubation	2.9α,β,δ	2.167α	2.233α
PoT120-120 min after extubation	2	2	2

αP<0.05 (compared to baseline), βP<0.05 (Group D vs. Group P), δP<0.05 (Group D vs. group C), εP<0.05 (Group C vs. Group P)

There was a significant reduction in VAS scores in all the groups at 60 and 120 min after extubation as compared to VAS score at 15 min after extubation (P = 0.000). Mean VAS score was found to be significantly lower in Group D as compared to Group P (P = 0.0001), and this, in turn, was significantly lower than in Group C (P = 0.0001) at 15 min after extubation. Mean VAS score in Group D was significantly lower than in Groups P and C at 60 min after extubation (P = 0.0001) and in both Groups D and C as compared to Group P 120 min after extubation (P = 0.016) [Table 4].

Table 4

Postoperative mean visual analog scale scores

Time	Group D (dexmedetomidine)	Group P (pregabalin)	Group C (combination)
PoT15-15 min after extubation	1.767β,δ	2.6ε	3.133
PoT60-60 min after extubation	0.533α,β,δ	1.9α	1.967α
PoT120-120 min after extubation	0.4α,β	0.933α,ε	0.533α

αP<0.05 (compared to PoT15), βP<0.05 (Group D vs. Group P), δP<0.05 (Group D vs. Group C), εP<0.05 (Group C vs. Group P)

There was no significant difference in the incidence of side effects among the three groups. Three patients (10%) in Group D had bradycardia associated with hypotension in comparison with none in the other groups. This was reverted immediately after administration of intravenous atropine, and the difference was found to be statistically insignificant (P = 0.237288). No other side effects were observed in any of the groups.

DISCUSSION

In this study, we compared the efficacy of premedication with pregabalin, dexmedetomidine, and dexmedetomidine-pregabalin combination for attenuating the hemodynamic stress response and reducing anesthetic requirement in patients undergoing laparoscopic cholecystectomy. We could not find any study in literature comparing the effects of pregabalin and dexmedetomidine. Dexmedetomidine significantly reduced the stress response to laryngoscopy and intubation and pneumoperitoneum and decreased anesthetic requirement as compared to pregabalin and the combination groups. Dexmedetomidine was associated with significantly lower MAPs and higher sedation score in the preoperative and postoperative period and significantly lower HR and arterial pressures and reduced anesthetic requirement in the intraoperative period as compared to the other two groups. In addition, the time taken for extubation and to respond to verbal commands was longer and pain score was significantly less with dexmedetomidine. Patients in the combination group showed significantly higher sedation score in the preoperative period, reduced requirement of propofol, longer time for extubation and to respond to verbal commands after reversal, and had lower pain scores 2 h after extubation, as compared to the pregabalin group.

The pharmacological characteristics of dexmedetomidine, a highly selective α2 adrenoreceptor agonist, include sedation, anxiolysis, analgesia, and sympatholysis with anesthetic-sparing effects and absence of significant respiratory depression. These properties make dexmedetomidine suitable for sedation and analgesia in the perioperative period, as premedication, as an adjunct for general and regional anesthesia, and for postoperative sedation and analgesia.[4] Dexmedetomidine has been used intravenously as premedication in doses ranging from 0.2 to 2.5 μg/kg. Pregabalin, whose structure is similar to the GABA, possesses analgesic activity and is effective in preventing the neuropathic component of acute pain. Oral pregabalin has been used in doses ranging from 75 to 300 mg for premedication.

In the preoperative period, a significant reduction in HR and mean blood pressure was noted in all the groups after premedication, and this continued till induction. On comparing the three groups, we found that MAP was significantly lower in dexmedetomidine group as compared to pregabalin and the combination groups from 10 min before induction till the time of induction. Taittonen et al. who compared the effect of intramuscular clonidine (4 μg/kg) and IV dexmedetomidine (2.5 μg/kg) premedication (given 40–50 min before induction) found a significant reduction in HR and arterial pressures before induction in patients who had received dexmedetomidine.[5] Our results are similar to Gupta et al. who on comparing the effects of oral premedication with pregabalin 150 mg and clonidine 200 μg (given 75–90 min before surgery) found a reduction in HR and MAP in both the groups in the preoperative period.[6]

During the intraoperative period, a significant reduction in HR and mean blood pressure was noted in dexmedetomidine group in comparison to the baseline after laryngoscopy and tracheal intubation (LTI). Our results were similar to that of Menda et al. who used 1 μg/kg bolus of dexmedetomidine for attenuating hemodynamic response to endotracheal intubation and found that HR and MAP were significantly lower as compared to the baseline in the intraoperative period.[7] We found that dexmedetomidine was associated with a significantly lower HR before, during, and after pneumoperitoneum and a significantly lower MAP till the creation of pneumoperitoneum, as compared to baseline. In contrast, a significant rise in HR and arterial pressure was noted after laryngoscopy and intubation and before, during, and after pneumoperitoneum in the pregabalin and combination groups, and this persisted till the end of surgery. Our results are comparable to those of Gupta et al. who found an increase in MAP after LTI with pregabalin (150 mg given 75–90 min before induction).[6] On comparing the three groups, we found a significant decrease in HR after LTI and after creation of pneumoperitoneum with dexmedetomidine as compared to pregabalin and HR was significantly less with dexmedetomidine as compared to pregabalin and combination groups during the entire intraoperative period. Similarly, MAP was significantly less with dexmedetomidine as compared to the other two groups after LTI, before and after pneumoperitoneum and the entire intraoperative period. No difference in hemodynamics was found between pregabalin and combination groups.

In the postoperative period, a significant decrease in HR and MAP was noted as compared to the baseline in patients who received dexmedtomidine, in contrast to the other two groups in which a significant increase was noted after extubation. Although there was no significant difference in HR among the groups, blood pressure was significantly lower in the dexmedetomidine group as compared to pregabalin and their combination till 2 h after extubation. Our findings are similar to those of Bhattacharjee et al. who also found a significant reduction in HR and mean blood pressure postoperatively in patients receiving dexmedetomidine.[1]

Anesthetic requirement was less in patients who received dexmedetomidine. The average isoflurane dial concentration was significantly less with dexmedetomidine as compared to pregabalin and combination groups (33% and 31% reduction, respectively). Keniya et al. who evaluated the effect dexmedetomidine had on perioperative anesthetic requirement, also observed a decrease of 32% in average inspiratory concentration of isoflurane as compared to placebo.[8] A significant reduction in the dose of propofol was also noted in the dexmedetomidine group as compared to pregabalin (19%) and combination (10%) group and in the combination group as compared to pregabalin (10%) group. A mean dose of 0.63 μg/kg dexmedetomidine has been found to reduce the dose of propofol required for induction of anesthesia.[9] Significantly less number of patients required additional fentanyl in the dexmedetomidine group (10%) in comparison to the pregabalin (43%) group in our study. Bajwa et al. who evaluated the dose-sparing effect of opioids and anesthetics in patients undergoing elective surgery found that the requirement of fentanyl during the surgical period was significantly decreased in patients who were given dexmedetomidine preoperatively. This was similar to the results we obtained. Dexmedetomidine has been shown to have significant analgesic properties and consistently reduce the requirement of opioids. The mechanism of action is believed to be the activation of α2c-adrenoreceptor in the spinal cord, which increases the analgesic action of opioids by lowering the transmission of nociceptive signals to the brain. Its analgesic effect can also be attributed to the inhibition of the release of substance P from the dorsal horn of the spinal cord. Other authors who studied the analgesic efficacy of pregabalin found that cumulative opioid consumption was significantly decreased with 300 mg pregabalin or more (Zhang et al.). In our study, patients in the pregabalin group were given only 150 mg of pregabalin, hence the requirement for additional analgesia was significantly more as compared to dexmedetomidine.

In the preoperative period, sedation score was significantly higher after dexmedetomidine was given. Preoperative sedation score was significantly higher in the dexmedetomidine and combination groups as compared to the pregabalin group and in the dexmedetomidine group as compared to the combination group. Dexmedetomidine causes presynaptic activation of the α2A-adrenoceptors in the locus coeruleus which causes an inhibition in the release of NE which consequently results in sedation and hypnosis.[10]

Time taken for extubation and to respond to verbal commands after extubation, was significantly longer in patients who were given dexmedetomidine (both alone and in combination) as compared to the pregabalin group. This may be due to the sedative effects of dexmedetomidine. Zeyneloglu et al. compared the recovery profile and sedative effects of dexmedetomidine with midazolam-fentanyl and found that patients who were given dexmedetomidine had significantly longer recovery time.[11]

In the postoperative period, patients in all the groups had a higher sedation score as compared to the baseline. Patients who received dexmedetomidine alone had significantly more sedation as compared to those who received pregabalin or a combination of pregabalin and dexmedetomidine. However, patients who had received dexmedetomidine remained arousable and comfortable. Studies by other authors have also found postoperative sedation scores to be significantly higher with dexmedetomidine as compared to placebo.[12]

In our study, patients in the dexmedetomidine group had significantly lower postoperative pain scores in comparison to the pregabalin group till 120 min, and as compared to the combination group till 60 min after extubation. Venn et al. who studied the analgesic efficacy of dexmedetomidine given in a dose of 1 μg/kg which was followed by 0.2–0.7 μg/kg/h infusion in 105 postoperative patients[13] found that patients required a significantly reduced amount of midazolam and morphine postoperatively.

Our study was limited by the nonavailability of MAC and BIS monitoring. We, however, measured the dial concentration of isoflurane and calculated the anesthetic requirement. Estimating depth of anesthesia by changes in HR and MAP is not ideal when dexmedetomidine is used as it provides hemodynamic stability. BIS monitoring is a more objective approach in assessing the depth of anesthesia and anesthetic requirement.

CONCLUSION

Dexmedetomidine was more effective than pregabalin and the combination of pregabalin and dexmedetomidine in attenuating hemodynamic response to laryngoscopy and intubation and pneumoperitoneum and reducing anesthetic requirement in laparoscopic cholecystectomy. Dexmedetomidine also provides better sedation in the preoperative period and better sedation and analgesia postoperatively as compared to pregabalin and combination of pregabalin and dexmedetomidine.

Dexmedetomidine is a valuable adjunct to the technique of balanced anesthesia for maintaining hemodynamic stability. Based on the observations of our study, we would recommend the use of dexmedetomidine for attenuating the hemodynamic response and reducing anesthetic requirement. However, a cost–benefit analysis needs to be carried out in the developing world. Furthermore, its use in patients with comorbid conditions and high-risk cases needs further evaluation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.